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Sample records for aneuploidy including trisomy

  1. Beyond Trisomy 21: Additional Chromosomal Anomalies Detected through Routine Aneuploidy Screening

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    Amy Metcalfe

    2014-04-01

    Full Text Available Prenatal screening is often misconstrued by patients as screening for trisomy 21 alone; however, other chromosomal anomalies are often detected. This study aimed to systematically review the literature and use diagnostic meta-analysis to derive pooled detection and false positive rates for aneuploidies other than trisomy 21 with different prenatal screening tests. Non-invasive prenatal testing had the highest detection (DR and lowest false positive (FPR rates for trisomy 13 (DR: 90.3%; FPR: 0.2%, trisomy 18 (DR: 98.1%; FPR: 0.2%, and 45,X (DR: 92.2%; FPR: 0.1%; however, most estimates came from high-risk samples. The first trimester combined test also had high DRs for all conditions studied (trisomy 13 DR: 83.1%; FPR: 4.4%; trisomy 18 DR: 91.9%; FPR: 3.5%; 45,X DR: 70.1%; FPR: 5.4%; triploidy DR: 100%; FPR: 6.3%. Second trimester triple screening had the lowest DRs and highest FPRs for all conditions (trisomy 13 DR: 43.9%; FPR: 8.1%; trisomy 18 DR: 70.5%; FPR: 3.3%; 45,X DR: 77.2%; FPR: 9.3%. Prenatal screening tests differ in their ability to accurately detect chromosomal anomalies. Patients should be counseled about the ability of prenatal screening to detect anomalies other than trisomy 21 prior to undergoing screening.

  2. Multiple recurrence of trisomy 21 in two Bedouin families: Parental gonadal mosaicism or {open_quotes}aneuploidy{close_quotes} gene effect?

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    Farag, T.I.; Murthy, D.S.K. [Kuwait Medical Genetics Centre, Sulibikhat (Kuwait)

    1994-09-01

    Two unrelated multiplex Down syndrome families is reported in Kuwait among the highly inbred population with Bedouin ancestors. Each family showed recurrent aneuploidies in three sibs with regular trisomy 21. Recurrent regular trisomy 21 in two or more siblings of healthy, normal parents (parental age <35 years) occurs rarely. Several possible etiological factors for recurrent aneuploidy have been suggested. The recurrence risks for regular trisomy 21 based on livebirth and prenatal diagnosis data were estimated at 1% - 2% for young women. However, there are no estimates for multiple recurrence of regular trisomy 21 in the young parents (<35 years). Clustering of trisomy 21 and trisomy 18 have been observed in Bedouin tribal population. The possibility of parental gonadal mosaicism and/or a possibility of an {open_quotes}aneuploidy gene{close_quotes} effect should be considered in practical genetic counselling of families with multiple recurrence of trisomy 21.

  3. Noninvasive Fetal Trisomy (NIFTY test: an advanced noninvasive prenatal diagnosis methodology for fetal autosomal and sex chromosomal aneuploidies

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    Jiang Fuman

    2012-12-01

    Full Text Available Abstract Background Conventional prenatal screening tests, such as maternal serum tests and ultrasound scan, have limited resolution and accuracy. Methods We developed an advanced noninvasive prenatal diagnosis method based on massively parallel sequencing. The Noninvasive Fetal Trisomy (NIFTY test, combines an optimized Student’s t-test with a locally weighted polynomial regression and binary hypotheses. We applied the NIFTY test to 903 pregnancies and compared the diagnostic results with those of full karyotyping. Results 16 of 16 trisomy 21, 12 of 12 trisomy 18, two of two trisomy 13, three of four 45, X, one of one XYY and two of two XXY abnormalities were correctly identified. But one false positive case of trisomy 18 and one false negative case of 45, X were observed. The test performed with 100% sensitivity and 99.9% specificity for autosomal aneuploidies and 85.7% sensitivity and 99.9% specificity for sex chromosomal aneuploidies. Compared with three previously reported z-score approaches with/without GC-bias removal and with internal control, the NIFTY test was more accurate and robust for the detection of both autosomal and sex chromosomal aneuploidies in fetuses. Conclusion Our study demonstrates a powerful and reliable methodology for noninvasive prenatal diagnosis.

  4. Cognitive and medical features of chromosomal aneuploidy.

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    Hutaff-Lee, Christa; Cordeiro, Lisa; Tartaglia, Nicole

    2013-01-01

    This chapter describes the physical characteristics, medical complications, and cognitive and psychological profiles that are associated with chromosomal aneuploidy conditions, a group of conditions in which individuals are born with one or more additional chromosome. Overall, chromosomal aneuploidy conditions occur in approximately 1 in 250 children. Information regarding autosomal disorders including trisomy 21 (Down syndrome), trisomy 13 (Patau syndrome), and trisomy 18 (Edward syndrome) are presented. Sex chromosome aneuploidy conditions such as Klinefelter syndrome (47,XXY), XYY, trisomy X, and Turner syndrome (45,X), in addition to less frequently occurring tetrasomy and pentasomy conditions are also covered. Treatment recommendations and suggestions for future research directions are discussed.

  5. Cognitive and medical features of chromosomal aneuploidy.

    Science.gov (United States)

    Hutaff-Lee, Christa; Cordeiro, Lisa; Tartaglia, Nicole

    2013-01-01

    This chapter describes the physical characteristics, medical complications, and cognitive and psychological profiles that are associated with chromosomal aneuploidy conditions, a group of conditions in which individuals are born with one or more additional chromosome. Overall, chromosomal aneuploidy conditions occur in approximately 1 in 250 children. Information regarding autosomal disorders including trisomy 21 (Down syndrome), trisomy 13 (Patau syndrome), and trisomy 18 (Edward syndrome) are presented. Sex chromosome aneuploidy conditions such as Klinefelter syndrome (47,XXY), XYY, trisomy X, and Turner syndrome (45,X), in addition to less frequently occurring tetrasomy and pentasomy conditions are also covered. Treatment recommendations and suggestions for future research directions are discussed. PMID:23622175

  6. Prenatal diagnosis of a trisomy 7/trisomy 13 mosaicism

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    Huijsdens-van Amsterdam Karin

    2012-01-01

    Full Text Available Abstract Double aneuploidy mosaicism of two different aneuploidy cell lines is rare. We describe for the first time a double trisomy mosaicism, involving chromosomes 7 and 13 in a fetus presenting with multiple congenital anomalies. No evidence for chimerism was found by DNA genotyping. The origin of both trisomies are consistent with isodisomy of maternal origin. Therefore, it is most likely that the double trisomy mosaicism arose from two independent events very early in embryonic development. The trisomy 7 and 13 cells were shown to be of maternal origin.

  7. Aneuploidy Screening in Pregnancy.

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    Dashe, Jodi S

    2016-07-01

    Prenatal aneuploidy screening has changed dramatically in recent years with increases in the types of chromosomal abnormalities reliably identified and in the proportion of aneuploid fetuses detected. Initially, screening was available only for trisomies 21 and 18 and was offered only to low-risk pregnancies. Improved detection with the quadruple- and first-trimester multiple marker screens led to the option of aneuploidy screening for women 35 years of age and older. Cell-free DNA tests now screen for common autosomal trisomies and sex chromosome aneuploidies. Cell-free DNA screening is particularly effective in older women because of higher positive predictive values and lower false-positive rates. Integrated first- and second-trimester multiple marker tests provide specific risks for trisomies 21, 18, and possibly 13, and may detect an even wider range of aneuploidies. Given current precision in risk assessment, based on maternal age and preferences for screening or diagnostic tests, counseling has become more complex. This review addresses the benefits and limitations of available aneuploidy screening methods along with counseling considerations when offering them. PMID:27275786

  8. Aneuploidy and Skeletal Health

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    Kamalakar, Archana; Harris, John R.; McKelvey, Kent D.; Suva, Larry J.

    2014-01-01

    The normal human chromosome complement consists of 46 chromosomes comprising 22 morphologically different pairs of autosomes and one pair of sex chromosomes. Variations in either chromosome number and/or structure frequently result in significant mental impairment, and/or a variety of other clinical problems, among them, altered bone mass and strength. Chromosomal syndromes associated with specific chromosomal abnormalities are classified as either numerical or structural and may involve more than one chromosome. Aneuploidy refers to the presence of an extra copy of a specific chromosome, or trisomy, as seen in Down’s syndrome (trisomy 21), or the absence of a single chromosome, or monosomy, as seen in Turner syndrome (a single X chromosome in females: 45, X). Aneuploidies have diverse phenotypic consequences, ranging from severe mental retardation and developmental abnormalities to increased susceptibility to various neoplasms and premature death. In fact, trisomy 21 is the prototypical aneuploidy in humans, is the most common genetic abnormality associated with longevity and is one of the most widespread genetic causes of intellectual disability. In this review, the impact of trisomy 21 on the bone mass, architecture, skeletal health and quality of life of people with Down syndrome will be discussed. PMID:24980541

  9. Trisomy 13

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    ... artery at birth. There are often signs of congenital heart disease , such as: Abnormal placement of the heart toward ... almost immediately. Most infants with trisomy 13 have congenital heart disease. Complications may include: Breathing difficulty or lack of ...

  10. Fluorescence in situ hybridization in uncultured amniocytes for detection of aneuploidy in 4210 prenatal cases

    Institute of Scientific and Technical Information of China (English)

    JIA Chan-wei; WANG Shu-yu; MA Yan-min; LAN Yong-lian; SI Yan-mei; YU Lan; ZHOU Li-ying

    2011-01-01

    Background Almost all reported fluorescence in situ hybridization (FISH) kits for prenatal diagnosis use probes from foreign (non-Chinese) countries. The aim of this study was to analyze the reliability of domestic (Chinese) FISH probe sets to detect aneuploidies of chromosomes 13, 18, 21, X, and Y related to prenatal diagnosis in 4210 cases.Methods Cytogenetic karyotyping was carded out as a standard prenatal diagnostic test, and amniotic fluid cell interphase FISH analysis was performed using two sets of probes (centromeric probes for chromosomes 18, X, and Y,and locus-specific probes for chromosomes 13 and 21) provided by GP Medical Technologies, Beijing, China. Then we compared the two results and found the performance characteristics for informative FISH results of aneuploidies by the domestic kit probes.Results In 4210 cases, 4126 cases generated karyotype results and 133 abnormal karyotypes (including 97 aneuploidies) were found. The FISH results of 98 cases (among them, 31 cases gave normal cytogenetic results) were uninformative. The rate of abnormal cases was 3.2% (133/4126). For the abnormal karyotypes, the rate of aneuploidy was 72.9% (97/133). Among the 97 aneuploidies, there were 58 cases of trisomy 21 (58/97, 59.8%), four cases of trisomy 13, 23 cases of trisomy 18, and 12 cases of sex chromosomal aneuploidies. The total concordance of the two methods was 97.9% (95/97; two cases were mosaics that had a low percentage of abnormal cells), and the concordance of trisomy 21, 13, and 18 by the two methods was 100%.Conclusions The two sets of the domestic FISH kit probes are reliable for prenatal diagnosis. The results demonstrate that FISH is a rapid and accurate clinical method for prenatal identification of chromosome aneuploidies.

  11. Mosaic double aneuploidy (45,X/47,XX,+8) with aortic dissection.

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    Lee, M N; Choi, K H; Kim, D K; Kim, S H

    2014-01-01

    Chromosomal aneuploidy is considerably frequent and may involve either autosomes or sex chromosomes. While double aneuploidy involving both autosomal and sex chromosomes is rare, several reports described the cases of sex chromosomal aneuploidies in combination with trisomy 21, such as Down-Klinefelter and Down-Turner syndrome. However, trisomy 8-Turner syndrome has been rarely described to date. Here we report a case of a 28-year-old female with mosaic trisomy 8-Turner syndrome. The patient was referred to our hospital for aortic dissection. On physical evaluation, features of her phenotype, which included short stature, webbed neck and cubitus valgus, suggested congenital anomalies such as Turner syndrome. Chest CT revealed aortic dissection with bicuspid aortic valve and coarctation. G-banding cytogenetic analysis of peripheral blood showed mosaicism with two cell lines (45,X[17]/47,XX,+8[33]). FISH analysis indicated that 15% of the cells were of monosomy X karyotype and 85% of the cells were with XX karyotype and trisomy 8 was detected only in XX cells. Though the patient exhibited clinical features of Turner syndrome, somatic stigmas present were not clearly distinguishable from those of trisomy 8, such as short stature, skeletal and cardiac abnormalities. Observations from most of the double aneuploidy cases indicated that the patient's phenotype was not necessarily in correlation to the ratio of autosomal and sex chromosomal aberrations. Mosaicism in trisomy 8-Turner syndrome was rarely documented and we believe this is the first reported case of mosaicism in trisomy 8-Turner syndrome presenting with aortic dissection and surviving into adulthood.

  12. Mosaic double aneuploidy (45,X/47,XX,+8) with aortic dissection.

    Science.gov (United States)

    Lee, M N; Choi, K H; Kim, D K; Kim, S H

    2014-01-01

    Chromosomal aneuploidy is considerably frequent and may involve either autosomes or sex chromosomes. While double aneuploidy involving both autosomal and sex chromosomes is rare, several reports described the cases of sex chromosomal aneuploidies in combination with trisomy 21, such as Down-Klinefelter and Down-Turner syndrome. However, trisomy 8-Turner syndrome has been rarely described to date. Here we report a case of a 28-year-old female with mosaic trisomy 8-Turner syndrome. The patient was referred to our hospital for aortic dissection. On physical evaluation, features of her phenotype, which included short stature, webbed neck and cubitus valgus, suggested congenital anomalies such as Turner syndrome. Chest CT revealed aortic dissection with bicuspid aortic valve and coarctation. G-banding cytogenetic analysis of peripheral blood showed mosaicism with two cell lines (45,X[17]/47,XX,+8[33]). FISH analysis indicated that 15% of the cells were of monosomy X karyotype and 85% of the cells were with XX karyotype and trisomy 8 was detected only in XX cells. Though the patient exhibited clinical features of Turner syndrome, somatic stigmas present were not clearly distinguishable from those of trisomy 8, such as short stature, skeletal and cardiac abnormalities. Observations from most of the double aneuploidy cases indicated that the patient's phenotype was not necessarily in correlation to the ratio of autosomal and sex chromosomal aberrations. Mosaicism in trisomy 8-Turner syndrome was rarely documented and we believe this is the first reported case of mosaicism in trisomy 8-Turner syndrome presenting with aortic dissection and surviving into adulthood. PMID:25059016

  13. Double trisomy (48,XXX,+18) with features of Roberts syndrome

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    Descartes, M.; Longshore, J.W.; Crawford, E. [Univ. of Alabama, Birmingham, AL (United States)] [and others

    1994-09-01

    We report an infant with double trisomy 48,XXX,+18, who also displayed features of Roberts syndrome. All previously published cases with similar double trisomy have presented with features of trisomy 18 syndrome. The chromosome analysis done at birth revealed the double trisomy; parental chromosomes were normal. The proband presented with microbrachycephaly, unilateral cleft lip and palate, choanal atresia, midfacial capillary hemanioma, thin nares, shallow orbits, malformed ears, sparse hair, hypomelia of the upper limbs, rocker-bottom feet, auricular septal defect and agenesis of the corpus callosum. Characteristic features of Roberts syndrome included hypomelia, midfacial defects, and severe growth deficiency. Among the many different features reported in the literature for patients with trisomy 18 syndrome, the most consistent were growth deficiency, clenched fingers and congenital heart defects (e.g. VSD, ASD, PDA). Although some of our patient`s features such as cleft lip and cleft palate, low-set malformed ears, ASD, defects of the corpus callosum, choanal atresia, radial aplasia could also be seen in trisomy 18 syndrome (in 10-50% of the cases), her phenotype was more typical of Roberts syndrome because of symmetrical hypomelia and midfacial defects. Our patient`s chromosomes did not show premature separation of centromeric heterochromatin, a feature reported to occur in approximately one-half of individuals with Roberts syndrome. Sporadic aneuploidy involving different chromosomes has been found in lymphocyte cultures from some Roberts syndrome patients and is considered by some authors as a mitotic mutant. This aneuploidy is most likely to be chromosome gain. The simultaneous occurrence of trisomy X and 18 is extremely rare with only 11 cases having been reported in the literature. Our patient is unique since she has the double trisomy in addition to the characteristic features of Roberts syndrome.

  14. Screening performance for trisomy 21 comparing first trimester combined screening and a first trimester contingent screening protocol including ductus venosus and tricuspid flow

    DEFF Research Database (Denmark)

    Ekelund, C K; Petersen, O B; Sundberg, K;

    2012-01-01

    To compare the standard first trimester combined risk assessment for trisomy 21 with a contingent screening protocol including tricuspid flow and ductus venosus flow.......To compare the standard first trimester combined risk assessment for trisomy 21 with a contingent screening protocol including tricuspid flow and ductus venosus flow....

  15. Specific transcriptional changes in human fetuses with autosomal trisomies.

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    Altug-Teber, O; Bonin, M; Walter, M; Mau-Holzmann, U A; Dufke, A; Stappert, H; Tekesin, I; Heilbronner, H; Nieselt, K; Riess, O

    2007-01-01

    Among full autosomal trisomies, only trisomies of chromosome 21 (Down syndrome), 18 (Edwards syndrome) and 13 (Patau syndrome) are compatible with postnatal survival. But the mechanisms, how a supernumerary chromosome disrupts the normal development and causes specific phenotypes, are still not fully explained. As an alternative to gene dosage effect due to the trisomic chromosome a genome-wide transcriptional dysregulation has been postulated. The aim of this study was to define the transcriptional changes in trisomy 13, 18, and 21 during early fetal development in order to obtain more insights into the molecular etiopathology of aneuploidy. Using oligonucleotide microarrays, we analyzed whole genome expression profiles in cultured amniocytes (AC) and chorionic villus cells (CV) from pregnancies with a normal karyotype and with trisomies of human chromosomes 13, 18 and 21. We observed a low to moderate up-regulation for a subset of genes of the trisomic chromosomes. Transcriptional levels of most of the genes on the supernumerary chromosome appeared similar to the respective chromosomal pair in normal karyotypes. A subset of chromosome 21 genes including the DSCR1 gene involved in fetal heart development was consistently up-regulated in different prenatal tissues (AC, CV) of trisomy 21 fetuses whereas only minor changes were found for genes of all other chromosomes. In contrast, in trisomy 18 vigorous downstream transcriptional changes were found. Global transcriptome analysis for autosomal trisomies 13, 18, and 21 supported a combination of the two major hypotheses. PMID:18253026

  16. Aneuploidy in Early Miscarriage and its Related Factors

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    Chan-Wei Jia

    2015-01-01

    Full Text Available Background: Genetic factors are the main cause of early miscarriage. This study aimed to investigate aneuploidy in spontaneous abortion by fluorescence in situ hybridization (FISH using probes for 13, 16, 18, 21, 22, X and Y chromosomes. Methods: A total of 840 chorionic samples from spontaneous abortion were collected and examined by FISH. We analyzed the incidence and type of abnormal cases and sex ratio in the samples. We also analyzed the relationship between the rate of aneuploidy and parental age, the rate of aneuploidy between recurrent abortion and sporadic abortion, the difference in incidence of aneuploidy between samples from previous artificial abortion and those from no previous induced abortion. Results: A total of 832 samples were finally analyzed. 368 (44.23% were abnormal, in which 84.24% (310/368 were aneuploidies and 15.76% (58/368 were polyploidies. The first was trisomy16 (121/310, followed by trisomy 22, and X monosomy. There was no significant difference in the rate of aneuploidy in the advanced maternal age group (≥35 years old and young maternal age group (<35 years old. However, the rate of trisomy 22 and the total rate of trisomies 21, 13, and 18 (the number of trisomy 21 plus trisomy 13 and trisomy 18 together showed significantly different in two groups. We found no skewed sex ratio. There was no significant difference in the rate of aneuploidy between recurrent miscarriage and sporadic abortion or between the samples from previous artificial abortion and those from no previous artificial abortion. Conclusions: Aneuploidy is a principal factor of miscarriage and total parental age is a risk factor. There is no skewed sex ratio in spontaneous abortion. There is also no difference in the rate of aneuploidy between recurrent abortion and sporadic abortion or between previous artificial abortion and no previous induced abortion.

  17. Aneuploidy among prenatally detected neural tube defects

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    Hume, R.F. Jr.; Lampinen, J.; Martin, L.S.; Johnson, M.P.; Evans, M.I. [Wayne State Univ., Detroit, MI (United States)] [and others

    1996-01-11

    We have reported previously a 10% aneuploidy detection rate among 39 cases of fetal neural tube defects (NTD). Subsequently we amassed an additional experience of over 17,000 prenatal diagnosis cases over a 5-year period. During this period 106 cases of NTDs were identified; 44 with anencephaly, 62 with open spina bifida. The average maternal age of this population with NTDs was 29 years (15-40); 6 patients declined amniocentesis. Six of 100 cytogenetic studies were aneuploid; on anencephalic fetus had inherited a maternal marker chromosome, and 5 NTD cases had trisomy 18. The average maternal age of the aneuploid cases was 21 (19-40); 3 were 35 years or older. Four of 5 trisomy 18 cases had multiple congenital anomalies (MCA). The overall aneuploidy detection rate in our cohort was 5-6, while aneuploidy occurred in 2% of the isolated NTD cases, and 24% of the MCA cases. Combining the earlier experience, 4/39 aneuploidy (2 trisomy 18, 4p+, del 13q) yields an aneuploidy detection frequency of 10/145 (7%), of which most (7/10) had trisomy 18. These data support fetal karyotyping for accurate diagnosis, prognosis, and recurrence-risk counseling. 5 refs., 2 tabs.

  18. Rapid screening for chromosomal aneuploidies using array-MLPA

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    van Beuningen Rinie

    2011-05-01

    Full Text Available Abstract Background Chromosome abnormalities, especially trisomy of chromosome 21, 13, or 18 as well as sex chromosome aneuploidy, are a well-established cause of pregnancy loss. Cultured cell karyotype analysis and FISH have been considered reliable detectors of fetal abnormality. However, results are usually not available for 3-4 days or more. Multiplex ligation-dependent probe amplification (MLPA has emerged as an alternative rapid technique for detection of chromosome aneuploidies. However, conventional MLPA does not allow for relative quantification of more than 50 different target sequences in one reaction and does not detect mosaic trisomy. A multiplexed MLPA with more sensitive detection would be useful for fetal genetic screening. Methods We developed a method of array-based MLPA to rapidly screen for common aneuploidies. We designed 116 universal tag-probes covering chromosomes 13, 18, 21, X, and Y, and 8 control autosomal genes. We performed MLPA and hybridized the products on a 4-well flow-through microarray system. We determined chromosome copy numbers by analyzing the relative signals of the chromosome-specific probes. Results In a blind study of 161 peripheral blood and 12 amniotic fluid samples previously karyotyped, 169 of 173 (97.7% including all the amniotic fluid samples were correctly identified by array-MLPA. Furthermore, we detected two chromosome X monosomy mosaic cases in which the mosaism rates estimated by array-MLPA were basically consistent with the results from karyotyping. Additionally, we identified five Y chromosome abnormalities in which G-banding could not distinguish their origins for four of the five cases. Conclusions Our study demonstrates the successful application and strong potential of array-MLPA in clinical diagnosis and prenatal testing for rapid and sensitive chromosomal aneuploidy screening. Furthermore, we have developed a simple and rapid procedure for screening copy numbers on chromosomes 13, 18

  19. Trisomy 13: Changing Perspectives.

    Science.gov (United States)

    Macias, Gabriel; Riley, Cheryl

    2016-01-01

    The diagnosis of trisomy 13 has been considered incompatible with life. Trisomy 13 is associated with a pattern of congenital anomalies and mental disabilities that make caring for these infants a challenge for both the family and health care professionals. The clinical management of trisomy 13 varies based on the organ systems involved. The current standard of care has been withholding intensive support and providing comfort care. Recent literature suggests there are improved outcomes in infants who receive intensive care at birth. In addition, case reports evaluating older children with trisomy 13 report that, although there are significant intellectual and psychomotor disabilities, these children do meet developmental milestones such as smiling in response to parents, sitting unassisted, and walking with a walker. This case review will include a discussion of the clinical course of an infant born with mosaic trisomy 13 where the parents requested intensive care. PMID:26842537

  20. Trisomy 13: Changing Perspectives.

    Science.gov (United States)

    Macias, Gabriel; Riley, Cheryl

    2016-01-01

    The diagnosis of trisomy 13 has been considered incompatible with life. Trisomy 13 is associated with a pattern of congenital anomalies and mental disabilities that make caring for these infants a challenge for both the family and health care professionals. The clinical management of trisomy 13 varies based on the organ systems involved. The current standard of care has been withholding intensive support and providing comfort care. Recent literature suggests there are improved outcomes in infants who receive intensive care at birth. In addition, case reports evaluating older children with trisomy 13 report that, although there are significant intellectual and psychomotor disabilities, these children do meet developmental milestones such as smiling in response to parents, sitting unassisted, and walking with a walker. This case review will include a discussion of the clinical course of an infant born with mosaic trisomy 13 where the parents requested intensive care.

  1. Double and multiple chromosomal aneuploidies in spontaneous abortions: A single institutional experience

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    Shivakumar Subramaniyam

    2014-01-01

    Full Text Available Objective: To characterize double and multiple aneuploidies in spontaneous abortions (SAB. Materials and Methods: Retrospective analysis of cytogenetics data obtained by culturing/harvesting products of the conception material at our center from 2006 to 2009 was performed. The abnormal cytogenetic results, maternal age, gestational age, and previous pregnancy history were recorded and compared. Results: Double and multiple aneuploidies are rare, however, a high percentage of double (4.6% and multiple (0.4% chromosomal aneuploidies were observed in our study of 1502 cases of SAB. Of 1502 cases of SAB evaluated, 70 cases (4.6% showed double aneuploidy, whereas 6 cases (0.4% had multiple aneuploidies. The chromosomes most frequently involved in double aneuploidy in the decreasing order were 21, 16, ± X, 22, 18, 13, and 15. The most frequent chromosome combinations observed were: Loss of X/21 (8.5%, 21/22 (4.4%, 16/21 (4.4%, and 7/16 (4.4%. The chromosome combinations in multiple aneuploidy included trisomy of chromosomes X/5/8, 8/20/22, 16/20/22, 14/21/22, and loss of X with 21/21 and 7/21. These abnormalities were significantly observed in women between the age group 40-44 years (59.2%. A high success rate (94% of obtaining metaphase cells was observed in this study mainly due to the use of direct and long-term cultures. Conclusions: We observed a high percentage of double (4.6% and multiple (0.4% aneuploidies, frequently involving the acrocentic chromosomes 13, 15, 21, and 22 and nonacrocentric chromosomes X, 16, and 18.

  2. First trimester screening for trisomy 21 in gestational week 8-10 by ADAM12-S as a maternal serum marker

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    Guitton Marie

    2010-10-01

    Full Text Available Abstract Background A disintegrin and metalloprotease 12 (ADAM12-S has previously been reported to be significantly reduced in maternal serum from women with fetal aneuploidy early in the first trimester and to significantly improve the quality of risk assessment for fetal trisomy 21 in prenatal screening. The aim of this study was to determine whether ADAM12-S is a useful serum marker for fetal trisomy 21 using the mixture model. Method In this case control study ADAM12-S was measured by KRYPTOR ADAM12-S immunoassay in maternal serum from gestational weeks 8 to 11 in 46 samples of fetal trisomy 21 and in 645 controls. Comparison of sensitivity and specificity of first trimester screening for fetal trisomy 21 with or without ADAM12-S included in the risk assessment using the mixture model. Results The concentration of ADAM12-S increased from week 8 to 11 and was negatively correlated with maternal weight. Log MoM ADAM12-S was positively correlated with log MoM PAPP-A (r = 0.39, P Conclusion The data show moderately decreased levels of ADAM12-S in cases of fetal aneuploidy in gestational weeks 8-11. However, including ADAM12-S in the routine risk does not improve the performance of first trimester screening for fetal trisomy 21.

  3. Aneuploidy in Early Miscarriage and its Related Factors

    Institute of Scientific and Technical Information of China (English)

    Chan-Wei Jia; Li Wang; Yong-Lian Lan; Rui Song; Li-Yin Zhou; Lan Yu; Yang Yang

    2015-01-01

    Background:Genetic factors are the main cause of early miscarriage.This study aimed to investigate aneuploidy in spontaneous abortion by fluorescence in situ hybridization (FISH) using probes for 13,16,18,21,22,X and Y chromosomes.Methods:A total of 840 chorionic samples from spontaneous abortion were collected and examined by FISH.We analyzed the incidence and type of abnormal cases and sex ratio in the samples.We also analyzed the relationship between the rate of aneuploidy and parental age,the rate of aneuploidy between recurrent abortion and sporadic abortion,the difference in incidence of aneuploidy between samples from previous artificial abortion and those from no previous induced abortion.Results:A total of 832 samples were finally analyzed.368 (44.23%) were abnormal,in which 84.24% (310/368) were aneuploidies and 15.76% (58/368) were polyploidies.The first was trisomy16 (121/310),followed by trisomy 22,and X monosomy.There was no significant difference in the rate ofaneuploidy in the advanced maternal age group (≥35 years old) and young maternal age group (<35 years old).However,the rate oftrisomy 22 and the total rate oftrisomies 21,13,and 18 (the number oftrisomy 21 plus trisomy 13 and trisomy 18 together) showed significantly different in two groups.We found no skewed sex ratio.There was no significant difference in the rate of aneuploidy between recurrent miscarriage and sporadic abortion or between the samples from previous artificial abortion and those from no previous artificial abortion.Conclusions:Aneuploidy is a principal factor of miscarriage and total parental age is a risk factor.There is no skewed sex ratio in spontaneous abortion.There is also no difference in the rate of aneuploidy between recurrent abortion and sporadic abortion or between previous artificial abortion and no previous induced abortion.

  4. The trisomy 18 syndrome

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    Cereda Anna

    2012-10-01

    Full Text Available Abstract The trisomy 18 syndrome, also known as Edwards syndrome, is a common chromosomal disorder due to the presence of an extra chromosome 18, either full, mosaic trisomy, or partial trisomy 18q. The condition is the second most common autosomal trisomy syndrome after trisomy 21. The live born prevalence is estimated as 1/6,000-1/8,000, but the overall prevalence is higher (1/2500-1/2600 due to the high frequency of fetal loss and pregnancy termination after prenatal diagnosis. The prevalence of trisomy 18 rises with the increasing maternal age. The recurrence risk for a family with a child with full trisomy 18 is about 1%. Currently most cases of trisomy 18 are prenatally diagnosed, based on screening by maternal age, maternal serum marker screening, or detection of sonographic abnormalities (e.g., increased nuchal translucency thickness, growth retardation, choroid plexus cyst, overlapping of fingers, and congenital heart defects . The recognizable syndrome pattern consists of major and minor anomalies, prenatal and postnatal growth deficiency, an increased risk of neonatal and infant mortality, and marked psychomotor and cognitive disability. Typical minor anomalies include characteristic craniofacial features, clenched fist with overriding fingers, small fingernails, underdeveloped thumbs, and short sternum. The presence of major malformations is common, and the most frequent are heart and kidney anomalies. Feeding problems occur consistently and may require enteral nutrition. Despite the well known infant mortality, approximately 50% of babies with trisomy 18 live longer than 1 week and about 5-10% of children beyond the first year. The major causes of death include central apnea, cardiac failure due to cardiac malformations, respiratory insufficiency due to hypoventilation, aspiration, or upper airway obstruction and, likely, the combination of these and other factors (including decisions regarding aggressive care. Upper airway

  5. Undetected sex chromosome aneuploidy by chromosomal microarray.

    Science.gov (United States)

    Markus-Bustani, Keren; Yaron, Yuval; Goldstein, Myriam; Orr-Urtreger, Avi; Ben-Shachar, Shay

    2012-11-01

    We report on a case of a female fetus found to be mosaic for Turner syndrome (45,X) and trisomy X (47,XXX). Chromosomal microarray analysis (CMA) failed to detect the aneuploidy because of a normal average dosage of the X chromosome. This case represents an unusual instance in which CMA may not detect chromosomal aberrations. Such a possibility should be taken into consideration in similar cases where CMA is used in a clinical setting.

  6. Identification of trisomy 18, trisomy 13, and Down syndrome from maternal plasma.

    Science.gov (United States)

    Gekas, Jean; Langlois, Sylvie; Ravitsky, Vardit; Audibert, François; van den Berg, David-Gradus; Haidar, Hazar; Rousseau, François

    2014-01-01

    Current prenatal diagnosis for fetal aneuploidies (including trisomy 21 [T21]) generally relies on an initial biochemical serum-based noninvasive prenatal testing (NIPT) after which women who are deemed to be at high risk are offered an invasive confirmatory test (amniocentesis or chorionic villi sampling for a fetal karyotype), which is associated with a risk of fetal miscarriage. Recently, genomics-based NIPT (gNIPT) was proposed for the analysis of fetal genomic DNA circulating in maternal blood. The diffusion of this technology in routine prenatal care could be a major breakthrough in prenatal diagnosis, since initial research studies suggest that this novel approach could be very effective and could reduce substantially the number of invasive procedures. However, the limitations of gNIPT may be underappreciated. In this review, we examine currently published literature on gNIPT to highlight advantages and limitations. At this time, the performance of gNIPT is relatively well-documented only in high-risk pregnancies for T21 and trisomy 18. This additional screening test may be an option for women classified as high-risk of aneuploidy who wish to avoid invasive diagnostic tests, but it is crucial that providers carefully counsel patients about the test's advantages and limitations. The gNIPT is currently not recommended as a first-tier prenatal screening test for T21. Since gNIPT is not considered as a diagnostic test, a positive gNIPT result should always be confirmed by an invasive test, such as amniocentesis or chorionic villus sampling. Validation studies are needed to optimally introduce this technology into the existing routine workflow of prenatal care. PMID:25053891

  7. Rapid prenatal diagnosis of trisomy 21 by fluorescent quantitative multiplex polymerase chain reaction

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Trisomy 21, also named Down syndrome was the most frequent autosomal aneuploidy and the most common cause of mental retardation. Fifty percent patients had congenital heart malformation. Every 20 minutes one case of trisomy 21 was born, and the incidence rate was 1 in 600 to 800 newborns in China.1 In two thirds of cases with trisomy 21, there was a spontaneous abortion, so the actual incidence was higher than that obtained postnatally.

  8. Trisomy 18 (Edwards Syndrome

    Directory of Open Access Journals (Sweden)

    Masoud Poureisa

    2009-01-01

    Full Text Available Description and Definition "n"n Synonym: Edward syndrome Characterized by malformations of multiple organ systems, trisomy 18 has an incidence of 3 in 10000 live births. Abnormalities detectable by ultrasound Common findings Agenesis of the corpus callosum Choroid plexus cysts Posterior fossa abnormalities Micrognathia Low-set ears Microphthalmous Hypertelorism Short radial ray Clenched hand with overlapping index finger Clubbed foot Rocker-bottom foot Renal anomalies hydronephrosis Omphalocele Diaphragmatic hernia Cryptorchidism Heart defects Single umbilical artery Intrauterine growth restriction Polyhydramnios Nuchal lucency Occasional findings Meningomyelocele Ventriculomegaly Cleft lip and plate Major differential diagnoses Freeman-Sheldon syndrome (clenched hands and intrauterine growth restriction Pena Shokeir syndrome (pseudo-trisomy 18 Smith-Lemli-Opitz syndrome (clenched hands and intrauterine grown restriction Triploidy (intrauterine growth restriction Trisomy 9 Other multiple malformation syndromes associated with intrauterine growth retardation, limb anomalies and/ or heart defects. Ultrasound diagnosis Prenatal; ultrasound diagnosis has been established in the first trimester, based on the finding of a nuchal lucency. Detectable features on the early second trimester include abnormal forearms, clenched hands, clubbed feet, omphalocele and a major heart defect. The features of trisomy 18 are detectable in 80% of affected fetuses in the second trimester. Sonography is often used to evaluate fetuses for the prsence of trisomy 18 when choroid plexus cysts are present, or when the triple screen results in a low level of maternal serum alpha- fetoprotein, estriol and human chorionic  gonadotropin combination. Although trisomy 18 occurs in 1 in 100 fetuses with choroid plexus cysts, if it is an isolated finding, the risk for trisomy 18 falls below 1 in 400. Documenting an open hand is very helpful as most fetuses with trisomy 18 are

  9. Mosaic variegated aneuploidy with microcephaly: A rare cytogenetic syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Meck, J.M.; Kozma, C.; Stratakis, C. [Georgetown Univ. Medical Center, Washington, DC (United States)] [and others

    1994-09-01

    The term {open_quotes}mosaic variegated aneuploidy with microcephaly{close_quotes} describes the finding of a variety of chromosomal aneuploidies within the same individual. This mutation affecting mitotic segregation has been reported previously in only 7 persons. We report here on male and female siblings with this condition. Proband 1 died at 57 days of age; proband 2 is 7 months old. Amniocentesis performed on the first sibling only revealed multiple aneuploidies (+2, +6, +X, tetrasomy 2, double trisomy X and 11, and deletion Xq); the majority of cells were normal and the abnormal cells did not constitute true mosaicism. Postnatally, blood on proband 1 had 20/50 cells (40%) with +18, single cells with +10 and +20, and 28/50 normal cells (56%). This was initially interpreted as trisomy 18 mosaicism not detected in amniocytes. Blood from proband 2 showed the following; after 48 hrs in culture, 4/50 trisomic cells (+3, +6, +18, XXY); after 72 hrs 3/50 trisomic cells (+5, +6, +18); after 96 hrs, 7/50 aneuploid cells (+2, +8, +9, +10, +18, double trisomy 11 and 18, tetrasomy 2 with +18). Skin biopsy on proband 2 revealed trisomy 2 in 5/140 cells (4%), one cell each +18 and +19, on cell tetrasomy 2, one cell XXY and +5; 131 cells (94%) were normal. Paternal skin fibroblasts had trisomy 6 in 2/100 cells and 1 cell trisomy 5; the remainder were normal. One trisomic cell (+18) in 100 was found in maternal skin fibroblasts. Trisomy 18 was the most common aneuploidy in the probands` blood. Aneuploidy for chromosomes 2 and X were more common in amniocytes and skin. No trisomies of chromosomes 1, 4, 12-17, 22 or Y were observed; acrocentrics rarely malsegregated. These findings are consistent with those of the other 7 reported patients, and constitute a distinct syndrome of multiple chromosomal aneuploidies associated with microcephaly. Although rare, cytogeneticists and clinical geneticists should be aware of this mitotic mutant.

  10. Aneuploidy in stem cells

    OpenAIRE

    Garcia-Martinez, Jorge; Bakker, Bjorn; Schukken, Klaske M; Simon, Judith E; Foijer, Floris

    2016-01-01

    Stem cells hold enormous promise for regenerative medicine as well as for engineering of model systems to study diseases and develop new drugs. The discovery of protocols that allow for generating induced pluripotent stem cells (IPSCs) from somatic cells has brought this promise steps closer to reality. However, as somatic cells might have accumulated various chromosomal abnormalities, including aneuploidies throughout their lives, the resulting IPSCs might no longer carry the perfect bluepri...

  11. Rapid diagnosis of aneuploidy using segmental duplication quantitative fluorescent PCR.

    Directory of Open Access Journals (Sweden)

    Xiangdong Kong

    Full Text Available The aim of this study was use a simple and rapid procedure, called segmental duplication quantitative fluorescent polymerase chain reaction (SD-QF-PCR, for the prenatal diagnosis of fetal chromosomal aneuploidies. This method is based on the co-amplification of segmental duplications located on two different chromosomes using a single pair of fluorescent primers. The PCR products of different sizes were subsequently analyzed through capillary electrophoresis, and the aneuploidies were determined based on the relative dosage between the two chromosomes. Each primer set, containing five pairs of primers, was designed to simultaneously detect aneuploidies located on chromosomes 21, 18, 13, X and Y in a single reaction. We applied these two primer sets to DNA samples isolated from individuals with trisomy 21 (n = 36; trisomy 18 (n = 6; trisomy 13 (n = 4; 45, X (n = 5; 47, XXX (n = 3; 48, XXYY (n = 2; and unaffected controls (n = 40. We evaluated the performance of this method using the karyotyping results. A correct and unambiguous diagnosis with 100% sensitivity and 100% specificity, was achieved for clinical samples examined. Thus, the present study demonstrates that SD-QF-PCR is a robust, rapid and sensitive method for the diagnosis of common aneuploidies, and these analyses can be performed in less than 4 hours for a single sample, providing a competitive alternative for routine use.

  12. A study of aneuploidy and DNA fragmentation in spermatozoa of three men with sex chromosome mosaicism including a 45,X cell line.

    Science.gov (United States)

    Nguyen, Minh Huong; Morel, Frederic; Bujan, Louis; May-Panloup, Pascale; De Braekeleer, Marc; Perrin, Aurore

    2015-06-01

    Meiotic segregation of mosaic males with a 45,X cell line has been little examined. In this study, we evaluated the risk of aneuploid gametes using fluorescence in situ hybridization (FISH) and DNA fragmentation in ejaculated spermatozoa of three men with sex chromosome mosaicism including a 45,X cell line. Triple- and dual-color FISH were performed. Sperm DNA fragmentation was detected using the TUNEL assay. A significantly increased frequency of XY disomic spermatozoa was observed for patients (P)1 and P2. A significant increase in diploidy and autosomal aneuploidy was found in P2 and P3, respectively. The rate of DNA fragmentation was not different from that observed in a control group. Data from the literature are scarce (only 3 cases reported), making comparison of the present data difficult, especially as the frequencies of the cell lines comprising the mosaicism differed between patients. Furthermore, the proportion of the different cell lines can differ from one tissue to another in the same patient. Whether the relative levels of the several cell lines present in the mosaicism can influence the rate of aneuploid spermatozoa remains unknown.

  13. Effects of aneuploidy on genome structure, expression, and interphase organization in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Bruno Huettel

    2008-10-01

    Full Text Available Aneuploidy refers to losses and/or gains of individual chromosomes from the normal chromosome set. The resulting gene dosage imbalance has a noticeable affect on the phenotype, as illustrated by aneuploid syndromes, including Down syndrome in humans, and by human solid tumor cells, which are highly aneuploid. Although the phenotypic manifestations of aneuploidy are usually apparent, information about the underlying alterations in structure, expression, and interphase organization of unbalanced chromosome sets is still sparse. Plants generally tolerate aneuploidy better than animals, and, through colchicine treatment and breeding strategies, it is possible to obtain inbred sibling plants with different numbers of chromosomes. This possibility, combined with the genetic and genomics tools available for Arabidopsis thaliana, provides a powerful means to assess systematically the molecular and cytological consequences of aberrant numbers of specific chromosomes. Here, we report on the generation of Arabidopsis plants in which chromosome 5 is present in triplicate. We compare the global transcript profiles of normal diploids and chromosome 5 trisomics, and assess genome integrity using array comparative genome hybridization. We use live cell imaging to determine the interphase 3D arrangement of transgene-encoded fluorescent tags on chromosome 5 in trisomic and triploid plants. The results indicate that trisomy 5 disrupts gene expression throughout the genome and supports the production and/or retention of truncated copies of chromosome 5. Although trisomy 5 does not grossly distort the interphase arrangement of fluorescent-tagged sites on chromosome 5, it may somewhat enhance associations between transgene alleles. Our analysis reveals the complex genomic changes that can occur in aneuploids and underscores the importance of using multiple experimental approaches to investigate how chromosome numerical changes condition abnormal phenotypes and

  14. Trisomy 18 with unilateral atypical ectrodactyly

    Energy Technology Data Exchange (ETDEWEB)

    Rogers, R.C. [Greenwood Genetic Center, SC (United States)

    1994-01-01

    Becerra et al. recently reported on an infant with multiple congenital anomalies who had trisomy 18. This preterm infant presented with bilateral ectrodactyly of feet, small cleft palate, esophageal atresia with associated tracheoesophageal fistula, congenital heart disease and other anomalies. The authors referenced article by Castle and Bernstein, in which they reported a male with trisomy 18 and cleft foot as well as a review of the literature which showed 2 other infants with trisomy 18 and ectrodactyly of the feet. An additional case of trisomy 18 associated with multiple congenital anomalies, including unilaterial, atypical ectrodactyly of the left foot.

  15. Identification of trisomy 18, trisomy 13, and Down syndrome from maternal plasma

    Directory of Open Access Journals (Sweden)

    Gekas J

    2014-07-01

    Full Text Available Jean Gekas,1,2 Sylvie Langlois,3 Vardit Ravitsky,4 François Audibert,5 David-Gradus van den Berg,6 Hazar Haidar,4 François Rousseau2,71Prenatal Diagnosis Unit, Department of Medical Genetics and Pediatrics, Faculty of Medicine, Laval University, Québec City, Quebec, Canada; 2Department of Medical Biology, Centre Hospitalier Universitaire de Québec, Québec City, Quebec, Canada; 3Department of Medical Genetics, University of British Columbia, Vancouver, Canada; 4Bioethics Program, Department of Social and Preventive Medicine, School of Public Health, University of Montreal, Montreal, Canada; 5Department of Obstetrics and Gynecology, Sainte Justine Hospital, Montreal, Canada; 6Department of Social and Preventive Medicine, 7Department of Molecular Biology, Medical Biochemistry and Pathology, Faculty of Medicine, Laval University, Québec City, Quebec, CanadaAbstract: Current prenatal diagnosis for fetal aneuploidies (including trisomy 21 [T21] generally relies on an initial biochemical serum-based noninvasive prenatal testing (NIPT after which women who are deemed to be at high risk are offered an invasive confirmatory test (amniocentesis or chorionic villi sampling for a fetal karyotype, which is associated with a risk of fetal miscarriage. Recently, genomics-based NIPT (gNIPT was proposed for the analysis of fetal genomic DNA circulating in maternal blood. The diffusion of this technology in routine prenatal care could be a major breakthrough in prenatal diagnosis, since initial research studies suggest that this novel approach could be very effective and could reduce substantially the number of invasive procedures. However, the limitations of gNIPT may be underappreciated. In this review, we examine currently published literature on gNIPT to highlight advantages and limitations. At this time, the performance of gNIPT is relatively well-documented only in high-risk pregnancies for T21 and trisomy 18. This additional screening test may be an

  16. Rapid detection of autosomal aneuploidy using microsatellite markers

    Energy Technology Data Exchange (ETDEWEB)

    Ray, P.N.; Teshima, I.E. [Hospital for Sick Children, Ontario (Canada); Winsor, E.J.T. [Toronto Hospital, Ontario (Canada)] [and others

    1994-09-01

    Trisomy occurs in at least 4% of all clinically recognized pregnancies, making it the most common type of chromosome abnormality in humans. The most commonly occurring trisomies are those of chromosomes 13, 18, 21 and aneuploidy of X and Y, accounting for about 0.3% of all newborns and a much higher percentage of conceptuses. In Canada, prenatal chromosome analysis by amniocentesis is offered to those women {ge} 35 years of age at the time of delivery or equivalent risk by maternal serum screen. We are developing a rapid molecular diagnostic test to detect the most common autosomal aneuploidies in prenatal and neonatal samples. The tests makes use of highly polymorphic short tandem repeat markers labeled with fluorescent tags which allow analysis on a GENESCANNER automated fragment analyzer (ABI). Multiple polymorphic markers have been selected on each of chromosomes 13, 18 and 21. At a given locus, trisomic fetuses/neonates will have either three alleles or two alleles with one allele having twice the intensity of the other. Unaffected individuals have two equal intensity alleles. We are conducting a blind study that will compare the detection efficiencies of FISH analysis on uncultured cells and the molecular method on confirmation amniotic fluid samples collected at the time of termination of affected fetuses. Results on cultured amniocytes from one such patient confirmed that trisomy 21 can be detected. FISH was not done on this sample. In addition, detection efficiency of the molecular method in whole blood samples from affected neonates is also being studied. To date, two such samples have been tested, one with trisomy 13 and one with trisomy 18, and both samples were diagnosed correctly. Preliminary results suggest that this method may provide a valuable tool for the rapid diagnosis of aneuploidy.

  17. Detection of human aneuploidies in prenatal and postnatal diagnosis using molecular cytogenetics

    Directory of Open Access Journals (Sweden)

    Kucheria Kiran

    2002-01-01

    Full Text Available Chromosomal aneuploidies especially trisomies 13, 18, 21, monosomy X and 47, XXY account for up to 95% of live born cytogenetic abnormalities. The diagnosis of aneuploidies usually done by conventional cytogenetic analysis (CCA is associated with technical difficulties and requires about 1-3 weeks for providing a result, especially in prenatal diagnosis. In the present study, Fluorescence In Situ Hybridization (FISH was used on interphase cells for rapid prenatal and postnatal detection of aneuploidies. The frequent indications of high pregnancies included for prenatal diagnosis were previous child with chromosomal abnormalities, abnormal ultrasound scan and advanced maternal age (> 35 years. Interphase FISH was done using probes specific for chromosomes 13, 18, 21, X and Y on uncultured chorionic villi and amniotic fluid samples. All samples were analyzed subsequently using conventional cytogenetics. The analysis of aneuploidies for chromosomes 13, 15, 16, 18, 21, 22, X and Y using FISH was extended to abortuses from spontaneous abortion cases. In cases where cytogenetics was not informative, a diagnosis could be made using interphase FISH. For postnatal diagnosis, interphase FISH was done to confirm low-level mosaicism in patients with primary amenorrhea, suspected cases of Klinefelter syndrome, and mental retardation using probes specific for various autosomes, X and Y chromosomes. FISH was also done using probe specific for the sex-determining region (SRY on the Y chromosome in cases with ambiguous genitalia. The SRY region could be identified in cases that lacked the Y chromosome on conventional cytogenetic analysis thereby emphasizing on the high resolution of FISH technique in detecting sub-microscopic rearrangements. To conclude, interphase FISH decreases the time interval between sampling and diagnosis. This is of tremendous value in prenatal diagnosis of urgent high-risk pregnancies, management of ambiguous genitalia and low

  18. Aplastic Anemia in Two Patients with Sex Chromosome Aneuploidies.

    Science.gov (United States)

    Rush, Eric T; Schaefer, G Bradley; Sanger, Warren G; Coccia, Peter F

    2015-01-01

    Sex chromosome aneuploidies range in incidence from rather common to exceedingly rare and have a variable phenotype. We report 2 patients with sex chromosome aneuploidies who developed severe aplastic anemia requiring treatment. The first patient had tetrasomy X (48,XXXX) and presented at 9 years of age, and the second patient had trisomy X (47,XXX) and presented at 5 years of age. Although aplastic anemia has been associated with other chromosomal abnormalities, sex chromosome abnormalities have not been traditionally considered a risk factor for this condition. A review of the literature reveals that at least one other patient with a sex chromosome aneuploidy (45,X) has suffered from aplastic anemia and that other autosomal chromosomal anomalies have been described. Despite the uncommon nature of each condition, it is possible that the apparent association is coincidental. A better understanding of the genetic causes of aplastic anemia remains important.

  19. Trisomy 13 (Patau Syndrome

    Directory of Open Access Journals (Sweden)

    Masoud Poureisa

    2009-01-01

    Full Text Available "nDescription and Definition: Synonym: patau syndrome with an incidence of 1 in 5000 births, this syndrome is characterized by multiple congenital abnormalities involving virtually every organ system. "nAbnormalities Detectable by Ultrasound "nHoloprosencephaly "nVentriculomegaly "nEnlarged cisterna magna "nMicrocephaly "nAgenesis of the corpus callosum "nCleft lip and palate "nMidface hypoplasia "nCyclopia "nMicrophthalmia "nHypotelorism "nNuchal thickening "nNeural tube defect "nOmphalocele "nEchogenic, enlarged kidneys "nEchoic bowel "nEchogenic chordae tendinaea and single umbilical artery "nCardiac defects "nRadial aplasia "nPolydactyly "nFlexion deformity of the fingers "nMajor Differential Diagnoses "nMeckel-Gruber syndrome (polydactyly, neural tube defects and enlarged echogenic kidneys "nOther diagnostic possibilities vary, depending on the multiple abnormalities present in each affected fetus. "nUltrasound Diagnosis "nPrenatal sonographic detection has been established at as early as 12 weeks' gestation, based on the presence of holoprosencephaly. "nThe sonographic abnormalities (described earlier are easily detectable, owing to the severity of the defects and the multitude of organ systems involved. "nThe sensitivity of sonographic detection of trisomy 13 has been reported to be between 90% and 100% when a complete structural survey (including the heart is accomplished. "nIt is possible, although unusual, for a fetus with trisomy 13 syndome to have a completely normal structural survey in the second trimester. "nHeredity "nThis is an autosomal trisomic syndrome. "nNatural History and Outcome "nMost neonates with trisomy 13 die within hours or days of delivery. Eighty percent of affected babies die within the first month of life. "nOccasionally, survivors are reported; however, these individuals have profound mental retardation, seizures and failure to thrive. "nThose with trisomy 13 mosaicism may have a less severe clinical

  20. Non-invasive prenatal chromosomal aneuploidy testing--clinical experience: 100,000 clinical samples.

    Directory of Open Access Journals (Sweden)

    Ron M McCullough

    Full Text Available OBJECTIVE: As the first laboratory to offer massively parallel sequencing-based noninvasive prenatal testing (NIPT for fetal aneuploidies, Sequenom Laboratories has been able to collect the largest clinical population experience data to date, including >100,000 clinical samples from all 50 U.S. states and 13 other countries. The objective of this study is to give a robust clinical picture of the current laboratory performance of the MaterniT21 PLUS LDT. STUDY DESIGN: The study includes plasma samples collected from patients with high-risk pregnancies in our CLIA-licensed, CAP-accredited laboratory between August 2012 to June 2013. Samples were assessed for trisomies 13, 18, 21 and for the presence of chromosome Y-specific DNA. Sample data and ad hoc outcome information provided by the clinician was compiled and reviewed to determine the characteristics of this patient population, as well as estimate the assay performance in a clinical setting. RESULTS: NIPT patients most commonly undergo testing at an average of 15 weeks, 3 days gestation; and average 35.1 years of age. The average turnaround time is 4.54 business days and an overall 1.3% not reportable rate. The positivity rate for Trisomy 21 was 1.51%, followed by 0.45% and 0.21% rate for Trisomies 18 and 13, respectively. NIPT positivity rates are similar to previous large clinical studies of aneuploidy in women of maternal age ≥ 35 undergoing amniocentesis. In this population 3519 patients had multifetal gestations (3.5% with 2.61% yielding a positive NIPT result. CONCLUSION: NIPT has been commercially offered for just over 2 years and the clinical use by patients and clinicians has increased significantly. The risks associated with invasive testing have been substantially reduced by providing another assessment of aneuploidy status in high-risk patients. The accuracy and NIPT assay positivity rate are as predicted by clinical validations and the test demonstrates improvement in the

  1. Congenital anomalies associated with trisomy 18 or trisomy 13

    DEFF Research Database (Denmark)

    Springett, Anna; Wellesley, Diana; Greenlees, Ruth;

    2015-01-01

    The aim of this study was to examine the prevalence of trisomies 18 and 13 in Europe and the prevalence of associated anomalies. Twenty-five population-based registries in 16 European countries provided data from 2000-2011. Cases included live births, fetal deaths (20+ weeks' gestation), and term...

  2. First trimester PAPP-A in the detection of non-Down syndrome aneuploidy.

    Science.gov (United States)

    Ochshorn, Y; Kupferminc, M J; Wolman, I; Orr-Urtreger, A; Jaffa, A J; Yaron, Y

    2001-07-01

    Combined first trimester screening using pregnancy associated plasma protein-A (PAPP-A), free beta-human chorionic gonadotrophin, and nuchal translucency (NT), is currently accepted as probably the best combination for the detection of Down syndrome (DS). Current first trimester algorithms provide computed risks only for DS. However, low PAPP-A is also associated with other chromosome anomalies such as trisomy 13, 18, and sex chromosome aneuploidy. Thus, using currently available algorithms, some chromosome anomalies may not be detected. The purpose of the present study was to establish a low-end cut-off value for PAPP-A that would increase the detection rates for non-DS chromosome anomalies. The study included 1408 patients who underwent combined first trimester screening. To determine a low-end cut-off value for PAPP-A, a Receiver-Operator Characteristic (ROC) curve analysis was performed. In the entire study group there were 18 cases of chromosome anomalies (trisomy 21, 13, 18, sex chromosome anomalies), 14 of which were among screen-positive patients, a detection rate of 77.7% for all chromosome anomalies (95% CI: 55.7-99.7%). ROC curve analysis detected a statistically significant cut-off for PAPP-A at 0.25 MoM. If the definition of screen-positive were to also include patients with PAPP-AMoM, the detection rate would increase to 88.8% for all chromosome anomalies (95% CI: 71.6-106%). This low cut-off value may be used until specific algorithms are implemented for non-Down syndrome aneuploidy. PMID:11494288

  3. Partial trisomy 4q: a case report

    Institute of Scientific and Technical Information of China (English)

    CUI Ying-xia; WANG Yun-hua; HAO Li-jun; HOU Lin; LI Wei; HUANG Yun-feng

    2006-01-01

    @@ The clinical findings frequently presented in trisomy 4q syndrome including mental retardation, developmental delay and multiple abnormalities such as microcephaly, acrocephaly, as well as malformed ears, high/broad/depressed nasal bridge, teeth and thumb anomalies. It has been proposed that trisomy 4q is caused by a familial balanced translocation or a de novo imbalance. We reported a new case of trisomy 4q with a karyotype of 46, XY, der(5)t(4;5)(q27;q35) and this karyotye was reported for the first time.

  4. Unisexual and heterosexual meiotic reproduction generate aneuploidy and phenotypic diversity de novo in the yeast Cryptococcus neoformans.

    Directory of Open Access Journals (Sweden)

    Min Ni

    2013-09-01

    Full Text Available Aneuploidy is known to be deleterious and underlies several common human diseases, including cancer and genetic disorders such as trisomy 21 in Down's syndrome. In contrast, aneuploidy can also be advantageous and in fungi confers antifungal drug resistance and enables rapid adaptive evolution. We report here that sexual reproduction generates phenotypic and genotypic diversity in the human pathogenic yeast Cryptococcus neoformans, which is globally distributed and commonly infects individuals with compromised immunity, such as HIV/AIDS patients, causing life-threatening meningoencephalitis. C. neoformans has a defined a-α opposite sexual cycle; however, >99% of isolates are of the α mating type. Interestingly, α cells can undergo α-α unisexual reproduction, even involving genotypically identical cells. A central question is: Why would cells mate with themselves given that sex is costly and typically serves to admix preexisting genetic diversity from genetically divergent parents? In this study, we demonstrate that α-α unisexual reproduction frequently generates phenotypic diversity, and the majority of these variant progeny are aneuploid. Aneuploidy is responsible for the observed phenotypic changes, as chromosome loss restoring euploidy results in a wild-type phenotype. Other genetic changes, including diploidization, chromosome length polymorphisms, SNPs, and indels, were also generated. Phenotypic/genotypic changes were not observed following asexual mitotic reproduction. Aneuploidy was also detected in progeny from a-α opposite-sex congenic mating; thus, both homothallic and heterothallic sexual reproduction can generate phenotypic diversity de novo. Our study suggests that the ability to undergo unisexual reproduction may be an evolutionary strategy for eukaryotic microbial pathogens, enabling de novo genotypic and phenotypic plasticity and facilitating rapid adaptation to novel environments.

  5. Constitutional Mosaic Trisomy 13 in Two Germ Cell Layers is Different from Patau Syndrome? A Case Report.

    Science.gov (United States)

    Kunwar, Fulesh; Pandya, Vidhi; Bakshi, Sonal R

    2016-03-01

    The heterogeneous phenotype of known syndromes is a clinical challenge, and harmonized description using globally accepted ontology is desirable. This report attempts phenotypic analysis in a patient of constitutional mosaic trisomy 13 in mesoderm and ectoderm to make globally comparable clinical description. Phenotypic features (minor/major abnormalities) were recorded and matched with the Human Phenotype Ontology terms that were used to query web-based tool Phenomizer. We report here a case of 24-year-old girl born to non consanguineous parents with history of one abortion. Her phenotypic evaluation included short columella, low-set ears, seizures, enlarged naris, bifid tongue, infra-orbital fold, smooth philtrum, microtia, microcephaly, carious teeth, downslanted palpebral fissures, proportionate short stature, high palate, thin upper lip vermilion, small for gestational age, broad fingertip, broad hallux, mandibular prognathia and dental malocclusion. Karyotype and interphase FISH (Fluorescence in situ hybridization) was done in blood cells. Interphase FISH was also performed on buccal epithelial cells. Cytogenetic analysis demonstrated trisomy 13 mosaicism in 25% cells i.e. 47, XX,+13(9)/46,XX(27). The interphase FISH in blood cells showed trisomy 13 in 15%, whereas in buccal mucosa cells showed nearly 6%. Mosaic aneuploidy in constitutional karyotype can be responsible for variation in clinical and morphological presentation of patient with genetic disorder. PMID:27134897

  6. Proteomic profile determination of autosomal aneuploidies by mass spectrometry on amniotic fluids

    Directory of Open Access Journals (Sweden)

    Desmetz Caroline

    2008-01-01

    Full Text Available Abstract Background Prenatal diagnosis of chromosomal abnormalities by cytogenetic analysis is time-consuming, expensive, and requires highly qualified technicians. Rapid diagnosis of aneuploidies followed by reassurance of women with normal results can be performed by molecular analysis of uncultured foetal cells. In the present study, we developed a proteomic fingerprinting approach coupled with a statistical classification method to improve diagnosis of aneuploidies, including trisomies 13, 18, and 21, in amniotic fluid samples. Results The proteomic spectra obtained from 52 pregnant women were compiled, normalized, and mass peaks with mass-to-charge ratios between 2.5 and 50 kDa identified. Peak information was combined together and analysed using univariate statistics. Among the 208 expressed protein peaks, 40 differed significantly between aneuploid and non aneuploid samples, with AUC diagnostic values ranging from 0.71 to 0.91. Hierarchical clustering, principal component analysis and support vector machine (SVM analysis were performed. Two class predictor models were defined from the training set, which resulted in a prediction accuracy of 92.3% and 96.43%, respectively. Using an external and independent validation set, diagnostic accuracies were maintained at 87.5% and 91.67%, respectively. Conclusion This pilot study demonstrates the potential interest of protein expression signature in the identification of new potential biological markers that might be helpful for the rapid clinical management of high-risk pregnancies.

  7. Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood.

    Science.gov (United States)

    Fan, H Christina; Blumenfeld, Yair J; Chitkara, Usha; Hudgins, Louanne; Quake, Stephen R

    2008-10-21

    We directly sequenced cell-free DNA with high-throughput shotgun sequencing technology from plasma of pregnant women, obtaining, on average, 5 million sequence tags per patient sample. This enabled us to measure the over- and underrepresentation of chromosomes from an aneuploid fetus. The sequencing approach is polymorphism-independent and therefore universally applicable for the noninvasive detection of fetal aneuploidy. Using this method, we successfully identified all nine cases of trisomy 21 (Down syndrome), two cases of trisomy 18 (Edward syndrome), and one case of trisomy 13 (Patau syndrome) in a cohort of 18 normal and aneuploid pregnancies; trisomy was detected at gestational ages as early as the 14th week. Direct sequencing also allowed us to study the characteristics of cell-free plasma DNA, and we found evidence that this DNA is enriched for sequences from nucleosomes. PMID:18838674

  8. A review of trisomy X (47,XXX)

    OpenAIRE

    Sutherland Ashley; Howell Susan; Tartaglia Nicole R; Wilson Rebecca; Wilson Lennie

    2010-01-01

    Abstract Trisomy X is a sex chromosome anomaly with a variable phenotype caused by the presence of an extra X chromosome in females (47,XXX instead of 46,XX). It is the most common female chromosomal abnormality, occurring in approximately 1 in 1,000 female births. As some individuals are only mildly affected or asymptomatic, it is estimated that only 10% of individuals with trisomy X are actually diagnosed. The most common physical features include tall stature, epicanthal folds, hypotonia a...

  9. 产前超声检查在诊断染色体非整倍体异常胎儿中的价值%Application of prenatal ultrasound in the diagnosis of chromosomal aneuploidy abnormalities

    Institute of Scientific and Technical Information of China (English)

    钟惟娜; 邓学东

    2012-01-01

    目的 探讨产前超声检查在非整倍体异常胎儿诊断中的价值.方法 对2009年9月至2011年12月在我院经羊水细胞染色体核型分析诊断为非整倍体异常的24例胎儿产前超声异常声像图特征进行总结分析.结果 24例羊水细胞染色体核型分析确诊为非整倍体异常的胎儿中超声显示异常20例(83.3%,20/24),包括21-三体9例(9/13)、18-三体3例(3/3)、13-三体3例(3/3)、45,X 5例(5/5).其中单发畸形4例(20%,4/20),多发畸形13例(65%,13/20),仅表现为超声软标志异常3例(15%,3/20).18-三体、13-三体及45,X胎儿均有超声可检出的明显结构畸形或异常,21-三体胎儿3例,仅表现为超声软标志异常.24例非整倍体异常胎儿中以心脏畸形检出例数居多(41.7%,10/24),而颈部淋巴水囊瘤是45,X胎儿一个极其重要的超声标志.结论 非整倍体异常胎儿常伴有异常的超声声像图表现,部分还有相应的典型超声畸形谱,超声作为非侵入性检查技术对于非整倍体异常胎儿的诊断有重要临床意义.%Objective To investigate the clinical application of prenatal ultrasound in the diagnosis of chromosomal aneuploidy abnormalities . Methods Ultrasound imaging features in 24 aneuploidy abnormal fetuses which were diagnosed by amniocentesis in our hospital from September 2009 to December 2011 were analyzed retrospectively. Results Twenty -four cases of aneuploidy abnormalities dectected by amniocentesis were examined by prenatal ultrasound. Of these cases, twenty were found abnormalities , including 9 with trisomy 21,3 with trisomy 18,3 with trisomy 13 and 5 with 45 ,X monomer. Prenatal ultrasound showed single malformation in 4 cases, multi-malformation in 13 cases and separate ultrasonographic soft markers in 3 cases. Fetuses with trisomy 18,trisomy 13 and 45,X monomer were all had obvious structural abnormalities detected by ultrasound , otherwise, 3 cases of trisomy 21 had only ultrasonographic soft markers. In

  10. Constitutional aneuploidy and cancer predisposition†

    OpenAIRE

    Ganmore, Ithamar; Smooha, Gil; Izraeli, Shai

    2009-01-01

    Constitutional aneuploidies are rare syndromes associated with multiple developmental abnormalities and the alterations in the risk for specific cancers. Acquired somatic chromosomal aneuploidies are the most common genetic aberrations in sporadic cancers. Thus studies of these rare constitutional aneuploidy syndromes are important not only for patient counseling and clinical management, but also for deciphering the mechanisms by which chromosomal aneuploidy affect cancer initiation and progr...

  11. Role of Trisomy 21 Mosaicism in Sporadic and Familial Alzheimer's Disease.

    Science.gov (United States)

    Potter, Huntington; Granic, Antoneta; Caneus, Julbert

    2016-01-01

    Trisomy 21 and the consequent extra copy of the amyloid precursor protein (APP) gene and increased beta-amyloid (Aβ) peptide production underlie the universal development of Alzheimer's disease (AD) pathology and high risk of AD dementia in people with Down syndrome (DS). Trisomy 21 and other forms of aneuploidy also arise among neurons and peripheral cells in both sporadic and familial AD and in mouse and cell models thereof, reinforcing the conclusion that AD and DS are two sides of the same coin. The demonstration that 90% of the neurodegeneration in AD can be attributed to the selective loss of aneuploid neurons generated over the course of the disease indicates that aneuploidy is an essential feature of the pathogenic pathway leading to the depletion of neuronal cell populations. Trisomy 21 mosaicism also occurs in neurons and other cells from patients with Niemann-Pick C1 disease and from patients with familial or sporadic frontotemporal lobar degeneration (FTLD), as well as in their corresponding mouse and cell models. Biochemical studies have shown that Aβ induces mitotic spindle defects, chromosome mis-segregation, and aneuploidy in cultured cells by inhibiting specific microtubule motors required for mitosis. These data indicate that neuronal trisomy 21 and other types of aneuploidy characterize and likely contribute to multiple neurodegenerative diseases and are a valid target for therapeutic intervention. For example, reducing extracellular calcium or treating cells with lithium chloride (LiCl) blocks the induction of trisomy 21 by Aβ. The latter finding is relevant in light of recent reports of a lowered risk of dementia in bipolar patients treated with LiCl and in the stabilization of cognition in AD patients treated with LiCl. PMID:26651340

  12. Variable expressivity in Patau syndrome is not all related to trisomy 13 mosaicism.

    Science.gov (United States)

    Hsu, Hui-Fang; Hou, Jia-Woei

    2007-08-01

    Patau syndrome (trisomy 13) is very rare in live-born babies. Individuals with this chromosomal syndrome have a short lifespan and are rarely seen beyond infancy. This study is aimed at the clinical spectrum, natural history, and survival of patients with trisomy 13. We reviewed the detailed data of 13 Patau syndrome live-born babies. Among them two individuals were delivered from continuation of pregnancy even after prenatal diagnosis. The remaining 11 patients were born to younger mothers who did not undergo amniocentesis because no major anomalies except for cleft lip/palate were found on prenatal sonograms. The common features of Patau syndrome including the clinical triad (microphthalmia, cleft lip/palate, and polydactyly) and non-cyanotic heart defects were always found in our series. However, certain serious central defects (holoprosencephaly, omphalocele, and single umbilical artery), which are easily recognized from prenatal sonogram, occurred less frequently than those stated in the literature. The median survival time was 95 days and was longer than that previously reported. There were two infants with trisomic mosaicism with different outcomes in both clinical spectrum and survival. Otherwise, we also found the increased recurrence risks of aneuploidy in two individuals, and the longest survivor (84 months) of non-mosaic trisomy 13 in Taiwan. We thus suggest that long-term survival in our series is strongly correlated with different expressivity after prenatal selection, in addition to cytogenetic mosaicism. Less associated anomalies such as polyhydramnios, oligohydramnios, intrauterine growth retardation, single umbilical artery, eye defects, holoprosencephaly, omphalocele, and polycystic kidney may contribute to their clinical courses. PMID:17603803

  13. Origin of nondisjunction in trisomy 8 and trisomy 8 mosaicism.

    Science.gov (United States)

    Karadima, G; Bugge, M; Nicolaidis, P; Vassilopoulos, D; Avramopoulos, D; Grigoriadou, M; Albrecht, B; Passarge, E; Annerén, G; Blennow, E; Clausen, N; Galla-Voumvouraki, A; Tsezou, A; Kitsiou-Tzeli, S; Hahnemann, J M; Hertz, J M; Houge, G; Kuklík, M; Macek, M; Lacombe, D; Miller, K; Moncla, A; López Pajares, I; Patsalis, P C; Petersen, M B

    1998-01-01

    Causes of chromosomal nondisjunction is one of the remaining unanswered questions in human genetics. In order to increase our understanding of the mechanisms underlying nondisjunction we have performed a molecular study on trisomy 8 and trisomy 8 mosaicism. We report the results on analyses of 26 probands (and parents) using 19 microsatellite DNA markers mapping along the length of chromosome 8. The 26 cases represented 20 live births, four spontaneous abortions, and two prenatal diagnoses (CVS). The results of the nondisjunction studies show that 20 cases (13 maternal, 7 paternal) were probably due to mitotic (postzygotic) duplication as reduction to homozygosity of all informative markers was observed and as no third allele was ever detected. Only two cases from spontaneous abortions were due to maternal meiotic nondisjunction. In four cases we were not able to detect the extra chromosome due to a low level of mosaicism. These results are in contrast to the common autosomal trisomies (including mosaics), where the majority of cases are due to errors in maternal meiosis.

  14. Dysregulation of gene expression in the artificial human trisomy cells of chromosome 8 associated with transformed cell phenotypes.

    Directory of Open Access Journals (Sweden)

    Hisakatsu Nawata

    Full Text Available A change in chromosome number, known as aneuploidy, is a common characteristic of cancer. Aneuploidy disrupts gene expression in human cancer cells and immortalized human epithelial cells, but not in normal human cells. However, the relationship between aneuploidy and cancer remains unclear. To study the effects of aneuploidy in normal human cells, we generated artificial cells of human primary fibroblast having three chromosome 8 (trisomy 8 cells by using microcell-mediated chromosome transfer technique. In addition to decreased proliferation, the trisomy 8 cells lost contact inhibition and reproliferated after exhibiting senescence-like characteristics that are typical of transformed cells. Furthermore, the trisomy 8 cells exhibited chromosome instability, and the overall gene expression profile based on microarray analyses was significantly different from that of diploid human primary fibroblasts. Our data suggest that aneuploidy, even a single chromosome gain, can be introduced into normal human cells and causes, in some cases, a partial cancer phenotype due to a disruption in overall gene expression.

  15. Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood

    OpenAIRE

    Fan, H. Christina; Blumenfeld, Yair J.; Chitkara, Usha; Hudgins, Louanne; Quake, Stephen R.

    2008-01-01

    We directly sequenced cell-free DNA with high-throughput shotgun sequencing technology from plasma of pregnant women, obtaining, on average, 5 million sequence tags per patient sample. This enabled us to measure the over- and underrepresentation of chromosomes from an aneuploid fetus. The sequencing approach is polymorphism-independent and therefore universally applicable for the noninvasive detection of fetal aneuploidy. Using this method, we successfully identified all nine cases of trisomy...

  16. Germ-line transmission of trisomy 21: Data from 80 families suggest an implication of grandmaternal age and a high frequency of female-specific trisomy rescue

    Directory of Open Access Journals (Sweden)

    Kovaleva Natalia V

    2010-03-01

    Full Text Available Abstract Background Trisomy of chromosome 21 (T21; Down syndrome, DS is the most common aneuploidy in live births. Though its etiology has been intensively studied for a half of century, there are surprisingly many problems awaiting their elucidation. Some of the open questions are related directly to germ line mosaicism for T21, other problems include the prevalence of males with non-mosaic trisomy over females (skewed sex ratio, SR, the genetic predisposition to non-disjunction, etc. Studies in families of gonadal mosaicism (GM carriers might help resolving some of these problems. Results 80 families of carriers of GM, in which the sex of the offspring had been specified, were identified in the literature and in logbooks of two local genetic units. Mothers in these families were relatively young: only 8% of mothers were 35 years old and older at the time of delivery of their first affected offspring while the proportion of grandmothers on the GM carrier's side aged 35 years old and older was significantly higher (39%. Postzygotic rescue of T21 due to error in the meiosis I had been proposed as a mechanism of parental GM formation in 78% of the families with known origin of the T21. For the other 22%, rescue of errors in the meiosis II or postzygotic mitotic non-disjunction was assumed. Mosaicism for T21 in successive generations was reported in at least 12 families. The proportion of mosaics among affected female offspring (14% is significantly higher compared to that among affected male offspring (0%. Male preponderance (SR = 1.5 is found in non mosaic liveborn offspring with either maternally- or paternally transmitted T21. Among unaffected offspring of male carriers of GM there is a notable excess of females (SR = 0.27. Conclusion Both direct (results of cytogenetic and molecular study of the origin of trisomic line and indirect (advanced grandmaternal age on the side of GM carrier evidences allow to assume that significant proportion of

  17. Transient myeloproliferative disorder with partial trisomy 21.

    Science.gov (United States)

    Takahashi, Takahide; Inoue, Akira; Yoshimoto, Junko; Kanamitsu, Kiichiro; Taki, Tomohiko; Imada, Masahide; Yamada, Mutsuko; Ninomiya, Shinsuke; Toki, Tsutomu; Terui, Kiminori; Ito, Etsuro; Shimada, Akira

    2015-11-01

    Myeloid malignancy with Down syndrome (ML-DS) is estimated to have a step-wise leukemogenesis including GATA1 mutation. Trisomy 21 is essential for ML-DS; however, we do not know exactly which gene or genes located on chromosome 21 are necessary for the ML-DS. We report a female infant with transient myeloproliferative disorder (TMD) and partial trisomy 21. SNP array analysis showed 10 Mb amplification of 21q22.12-21q22.3, which included DYRK1A, ERG, and ETS but not the RUNX1 gene. With two other reported TMD cases having partial trisomy 21, DYRK1A, ERG, and ETS were the most likely genes involved in collaboration with the GATA1 mutation. PMID:26138905

  18. Modeling the Aneuploidy Control of Cancer

    Directory of Open Access Journals (Sweden)

    Wang Zhong

    2010-07-01

    Full Text Available Abstract Background Aneuploidy has long been recognized to be associated with cancer. A growing body of evidence suggests that tumorigenesis, the formation of new tumors, can be attributed to some extent to errors occurring at the mitotic checkpoint, a major cell cycle control mechanism that acts to prevent chromosome missegregation. However, so far no statistical model has been available quantify the role aneuploidy plays in determining cancer. Methods We develop a statistical model for testing the association between aneuploidy loci and cancer risk in a genome-wide association study. The model incorporates quantitative genetic principles into a mixture-model framework in which various genetic effects, including additive, dominant, imprinting, and their interactions, are estimated by implementing the EM algorithm. Results Under the new model, a series of hypotheses tests are formulated to explain the pattern of the genetic control of cancer through aneuploid loci. Simulation studies were performed to investigate the statistical behavior of the model. Conclusions The model will provide a tool for estimating the effects of genetic loci on aneuploidy abnormality in genome-wide studies of cancer cells.

  19. Specific grasp characteristics of children with trisomy 21.

    Science.gov (United States)

    Jover, Marianne; Ayoun, Catherine; Berton, Catherine; Carlier, Michèle

    2010-12-01

    Children with trisomy 21 display atypical manual skills that change to some extent during development. We examined grasp characteristics and their development in 35 children with trisomy 21, aged 4-18 years, who performed simple manual tasks (two manual tasks of the Movement Assessment Battery for Children, and grasping of five wooden blocks whose size was determined by their hand size). The age-matched comparison group included 35 typically developing children. Children with trisomy 21 were found to use fewer fingers than children in the comparison group in each task. They also used specific grasps and tended to extend fingers that were not involved in the grip. While some specific grasp characteristics of children with trisomy 21 decreased with age, other did not, and remained present throughout development. The perceptual-motor development of children with trisomy 21 should be analyzed in terms of atypical development rather than developmental delay. PMID:20564329

  20. [Introduction of noninvasive prenatal testing for fetal trisomies: preliminary results and consequences on invasive samplings].

    Science.gov (United States)

    Van Wymersch, D; Gilson, G

    2015-01-01

    Noninvasive prenatal testing (NIPT) has marked a revolution in aneuploidy screening because it allows a simple maternal blood test to detect trisomy 21, 18 and 13 in a foetus with a very high level of accuracy. After one year of NIPT utilisation with 683 samples, we analyzed retrospectively the performance of the test for 2014 : 3 positive samples (2 trisomies 21 and 1 trisomy 18) were correctly detected (100% sensitivity) and no foetal aneuploidy was missed for the pregnancies having already resulted in delivery by decembre 2014 (280 true negatif, 100% specificity). However, the additionnally available analysis of the sex chromosomes resulted in 2 erronous results: 1 uncorrect sex determination (1 male resulting in a female phenotype at birth) and 1 result suggesting a Turner syndrome was not confirmed by amniocentesis. The failure rate leading to a resampling was at 1.46% (10/683). The test used was the NIFTY of the BGI laboratory in Hong-Kong. By comparison to the year 2013, the utilisation of NIPT lead to a significant diminution of invasive samples performed by amniocentesis or choriocentesis 144 vs. 239 (- 63%). We confirmed that NIPT is a high-performance tool for the screening of the main foetal aneuploidies and report that during its first year of utilisation, 63% of invasive samples collected could be avoided. The test is expensive, not reimboursed by Luxembourg social security and therefore prohibitive for a number of women and their families. PMID:26946853

  1. 多重连接依赖探针扩增技术检测胎儿非整倍体染色体异常%Fetal aneuploidy detected by multiplex ligation-dependent probe amplification (MLPA)

    Institute of Scientific and Technical Information of China (English)

    吴琦嫦; 王文博; 江雨; 孔辉; 钟晓玲; 于威威; 孙丽; 周裕林

    2010-01-01

    Objective To investigate the role of muhiplex ligation-dependent probe amplification(MLPA) in identifying fetal aneuploidy of chromosomes 13,18,21,X,and Y. Methods From June 2007 to December 2008,263 samples(prenatal diagnosis group),including amniotic or umbilical cord blood from pregnant women who required prenatal diagnosis,were processed in parallel by MLPA and conventional karyotype to detect fetal aneuploidy.Another 26 samples(fetal death group).ineluding retained abortion and fetal death,were also processed bv MLPA. Results Five cases of 21-trisomy,4 eases of 18-trisomy,1 case of 13-trisomy and 3 cases of 45,X were identified among the prenatal diagnosis group by MLPA,and the results were consistent with karyotype.Two cases of 45,X and 1 case of 18-trisomy were identified among the retained abortion and fetal death group. Conclusions MLPA is a rapid,efficient,simple,reliable and economical technique in detecting most common chromosomal aneuploidies and have important clinical value.%目的 探讨多重连接依赖探针扩增技术(multiplex ligation-dependent probe amplifiea-tion,MLPA)在检测胎儿非整倍体染色体异常中的作用. 方法 2007年6月至2008年12月对263例需进行产前诊断的孕妇(产前诊断组)取羊水或脐血进行MLPA检测,同时进行传统的染色体核型分析.对26例发生稽留流产或死胎的孕妇取胎儿组织提取DNA进行MLPA检测. 结果 产前诊断组检出5例21-三体,4例18-三体,1例13-三体和3例45,X,与细胞核型分析结果一致.稽留流产或死胎组检出2例45,x和1例18-三体. 结论 MLPA可用于检测胎儿最常见的13、18、21、X、Y染色体非整倍体异常,用于产前诊断,快速简单,准确经济,有一定的临床推广价值.

  2. Non-invasive prenatal detection of trisomy 13 using a single nucleotide polymorphism- and informatics-based approach.

    Directory of Open Access Journals (Sweden)

    Megan P Hall

    Full Text Available PURPOSE: To determine how a single nucleotide polymorphism (SNP- and informatics-based non-invasive prenatal aneuploidy test performs in detecting trisomy 13. METHODS: Seventeen trisomy 13 and 51 age-matched euploid samples, randomly selected from a larger cohort, were analyzed. Cell-free DNA was isolated from maternal plasma, amplified in a single multiplex polymerase chain reaction assay that interrogated 19,488 SNPs covering chromosomes 13, 18, 21, X, and Y, and sequenced. Analysis and copy number identification involved a Bayesian-based maximum likelihood statistical method that generated chromosome- and sample-specific calculated accuracies. RESULTS: Of the samples that passed a stringent DNA quality threshold (94.1%, the algorithm correctly identified 15/15 trisomy 13 and 49/49 euploid samples, for 320/320 correct copy number calls. CONCLUSIONS: This informatics- and SNP-based method accurately detects trisomy 13-affected fetuses non-invasively and with high calculated accuracy.

  3. New insights on the origin and relevance of aneuploidy in human spermatozoa.

    Science.gov (United States)

    Templado, C; Uroz, L; Estop, A

    2013-10-01

    In humans, the most common chromosomal abnormality is aneuploidy. Because the majority of aneuploid conceptuses die during the early stages of embryonic development, an accurate estimate of the frequency of aneuploidy at conception can only be assessed by directly studying the gametes. The vast majority of aneuploidies arise de novo as a result of sporadic chromosome missegregation in paternal or maternal meiosis. In this review, we present the basic current knowledge about the incidence of aneuploidy in human spermatozoa in the general population and in patient populations where elevated levels of sperm aneuploidy are observed. These include infertile patients, patients with abnormal somatic karyotypes, and individuals exposed to certain environmental/lifestyle hazards. The clinical impact of increased levels of aneuploidy is discussed. We then focus on the non-disjunction mechanisms that cause aneuploidy during spermatogenesis and the factors that predispose to non-disjunction in male germ cells followed by an analysis of the sex differences in the incidence of gamete aneuploidy. Recent meiotic studies using multiplex-FISH on three fertile men have revealed that the frequency of conservative aneuploidy of metaphase II spermatocytes is similar to that observed in non-inseminated oocytes of young women. These findings suggest that the differences in the incidence of aneuploidy between spermatozoa and oocytes are not due to differences in chromosome segregation errors but rather to more effective checkpoint mechanisms in spermatogenesis than in oogenesis.

  4. Greater trochanteric stippling in trisomy 7p

    Energy Technology Data Exchange (ETDEWEB)

    Wilde, Justin R. [Starship Children' s Hospital, Department of Paediatrics, Auckland (New Zealand); Teele, Rita L. [Starship Children' s Hospital, Department of Radiology, Auckland (New Zealand); Aftimos, Salim [Auckland City Hospital, Northern Regional Genetic Services, Auckland, Private Bag 92024 (New Zealand)

    2006-08-15

    Trisomy 7p is a rare condition involving partial or complete duplication of the short arm of chromosome 7. Radiological features include large fontanelles, widened sutures, dolicocephaly and asymmetrical skull. We report a new radiological finding of punctate calcifications in the region of femoral trochanters. This finding has not previously been reported with chromosome 7p duplication. (orig.)

  5. Mosaic Trisomy 18 in a Five-Month-Old Infant

    Directory of Open Access Journals (Sweden)

    Ana Laura Fitas

    2013-01-01

    Full Text Available Individuals with mosaic trisomy 18, only approximately 5% of all trisomy 18 cases, carry both a trisomy 18 and an euploid cell line. Their clinical findings are highly variable, from the absence of dysmorphic features to the complete trisomy 18 syndrome. A five-month-old daughter of a 38-year-old mother, with vomiting and feeding problems, was referred to our department. She was undernourished and had axial hypotony and developmental delay, an irregular pattern of hypopigmentation on the right side of the abdomen, and moderate sagittal body asymmetry with left-side muscular hemihypotrophy. Mild craniofacial dysmorphy included dolichocephaly, frontal bossing, prominent occiput, long downslanting palpebral fissures, hypertelorism, and retrognathia. A complex heart defect with atrial and ventricular septal defects, pulmonary artery stenosis, and bicuspid aortic valve was identified. Cytogenetic analysis revealed mosaic trisomy 18 with trisomy in 90% of peripheral lymphocytes and 17% of skin fibroblasts. This case adds to our knowledge of the phenotypic spectrum and the natural history of mosaic trisomy 18 by adding a dysmorphic feature and a cardiac abnormality that, to the best of our knowledge, had not been previously described.

  6. Mosaicism most likely accounts for extended survival of trisomy 22

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, W.P.; Kalousek, D.K. [Univ. of British Columbia (Canada)

    1996-03-01

    This {open_quotes}Letter to the Editor{close_quotes} discusses the implications of meiotic versus somatic chromosomal aberrations and how this corresponds to the discussion of trisomy 22, including the survival time of the patient. 5 refs.

  7. Mosaic variegated aneuploidy associated with a dysmorphic syndrome and mental handicap

    Energy Technology Data Exchange (ETDEWEB)

    Mehta, L.; Babu, A.; Willner, J. [Sount Sinai Sachool of Medicine, New York, NY (United States)] [and others

    1994-09-01

    A 41-year-old woman was evaluated for dysmorphic features and mental handicap. Prior karyotyping had revealed 7% mosaicism for trisomy 18 in skin fibroblasts with normal blood chromosomes. Clinical features consisted of short stature, mild mental retardation, sensorineural deafness and the following dysmorphic features: short, broad neck, low posterior hairline, small palpebral fissures with iris coloboma on the right, epicanthic folds, small mouth, high palate and prominent mandible, short metacarpals and digits, particularly the fifth, with bilateral simian creases. Medical problems included non-insulin dependent diabetes mellitus, hypertension, oligomenorrhea and recent onset of diabetic neuropathy and retinal exudates. Head size and brain MRI were within normal limits. Peripheral blood chromosomes revealed: 46,XX (45 cells), 46,XX,t(7;16)(q21;q21) in 1 cell, 45,X (1 cell), 48,XXXX (1 cell), 47,XX,+mar (1 cell), 48,XX,+mar,+mar (1 cell). Skin fibroblasts revealed the following karyotypes: 46,XX (25 cells), 45,X (14 cells), 47,XX,+2 (10 cells) and 47,X,+2,+7 (1 cell). Previously reported cases of mosaic variegated aneuploidy include microcephaly as a prominent feature. Chromosomes involved in the abnormality are variable. Clinical presentations in such patients are not consistent and do not appear to correlate with specific chromosome defects. This patient represents an interesting example of probable mitotic instability disrupting normal developmental processes.

  8. Screening for aneuploidies by maternal age, fetal nuchal translucency and maternal serum biochemistry at 11-13+6 gestational weeks

    Directory of Open Access Journals (Sweden)

    Karadžov-Orlić Nataša

    2012-01-01

    Full Text Available Introduction. Aneuploidies are the major cause of perinatal death and early psychophysical disorders. Objective. In this study, we analyzed detection and false-positive rates of screening for aneuploidies in the first trimester by the combination of maternal age, fetal nuchal translucency (NT thickness and maternal serum free beta-human chorionic gonadotrophin (β-hCG, and pregnancy-associated plasma protein-A (PAPP-A at 11-13+6 weeks of gestation, using the appropriate software developed by the Fetal Medicine Foundation. Methods. Our screening study for aneuploidies analyzed 4172 singleton pregnancies from January 2006 to December 2010. The sensitivities and false-positive rates using the combined aneuploidies determination for the risk cut-off of 1:275 were evaluated. Results. In the trisomy 21 pregnancies, the fetal NT was higher than 95th centile, in 72.8%, serum free b-hCG concentration it was above the 95th centile in 55% and serum PAPP-A was below the 5th centile in 47% of the cases. In the trisomy 18 and 13, the fetal NT was above 95th centile in 66.6% and 44.4% of the cases, respectively. The serum free b-hCG concentration was above the 95th centile in 0 and 10%, but serum PAPP-A was below 5th centile in 80.9% and 88.8% of pregnancies. In the trisomy 21 pregnancies the median free beta-hCG was 2.3 MoM and the median PAPP-A was 0.45 MoM. Chromosomal abnormalities were detected in 169 fetuses: trisomy 21 (97, Turner syndrome (19, trisomy 18 (28, trisomy 13 (11 and others (14. Detection rate of combined screening for aneuploides were 86.0% with false positive rate of 5.3% (mean age 33±4.9 years, >35 years in 35% of pregnancies. Conclusion. Our study suggests that the strategy of first-trimester combined screening of biochemical values and ultrasonographic parameters at 12 gestational weeks identifies higher percentage of aneuploidies with a lower false-positive rate than a single parameter strategy.

  9. Transcriptional consequence and impaired gametogenesis with high-grade aneuploidy in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Kuan-Lin Lo

    Full Text Available Aneuploidy features a numerical chromosome variant that the number of chromosomes in the nucleus of a cell is not an exact multiple of the haploid number, which may have an impact on morphology and gene expression. Here we report a tertiary trisomy uncovered by characterizing a T-DNA insertion mutant (aur2-1/+ in the Arabidopsis (Arabidopsis thaliana AURORA2 locus. Whole-genome analysis with DNA tiling arrays revealed a chromosomal translocation linked to the aur2-1 allele, which collectively accounted for a tertiary trisomy 2. Morphologic, cytogenetic and genetic analyses of aur2-1 progeny showed impaired male and female gametogenesis to various degrees and a tight association of the aur2-1 allele with the tertiary trisomy that was preferentially inherited. Transcriptome analysis showed overlapping and distinct gene expression profiles between primary and tertiary trisomy 2 plants, particularly genes involved in response to stress and various types of external and internal stimuli. Additionally, transcriptome and gene ontology analyses revealed an overrepresentation of nuclear-encoded organelle-related genes functionally involved in plastids, mitochondria and peroxisomes that were differentially expressed in at least three if not all Arabidopsis trisomics. These observations support a previous hypothesis that aneuploid cells have higher energy requirement to overcome the detrimental effects of an unbalanced genome. Moreover, our findings extend the knowledge of the complex nature of the T-DNA insertion event influencing plant genomic integrity by creating high-grade trisomy. Finally, gene expression profiling results provide useful information for future research to compare primary and tertiary trisomics for the effects of aneuploidy on plant cell physiology.

  10. Trisomy 8 in leukemia: A GCRI experience

    Directory of Open Access Journals (Sweden)

    Sonal R Bakshi

    2012-01-01

    Full Text Available Trisomy of chromosome 8 is frequently reported in myeloid lineage disorders and also detected in lymphoid neoplasms as well as solid tumors suggesting its role in neoplastic progression in general. It is likely to be a disease-modulating secondary event with underlying cryptic aberrations as it has been frequently reported in addition to known abnormalities contributing to clinical heterogeneity and modifying prognosis. Here, we share our findings of trisomy 8 in leukemia patients referred for diagnostic and prognostic cytogenetic assessment. Total 60 cases of trisomy 8, as a sole anomaly or in addition to other chromosomal aberrations, were reported (January 2005-September 2008. Unstimulated bone marrow or blood samples were cultured, followed by GTG banding and karyotyping as per the ISCN 2005. Patients with +8 were chronic myeloid leukemia (CML (36, acute myeloid leukemia (AML (17, and acute lymphoblastic leukemia (ALL (7. In 7 patients, trisomy 8 was the sole anomaly, whereas in 6 patients +8 was in addition to normal clone, in 47 patients, the +8 was in addition to t(9;22, t(15;17, and others, including 3 with tetrasomy 8. Only one patient showed constitutional +8. The present study will form the basis of further cumulative studies to correlate potential differential effects of various karyotypic anomalies on disease progression and survival following a therapeutic regime. To unravel the role of extra 8 chromosome, constitutional chromosomal analysis and uniparental disomy will be considered.

  11. Fetal ultrasound findings in trisomy 18 at midpregnancy

    Directory of Open Access Journals (Sweden)

    Petrović Bojana

    2015-01-01

    Full Text Available Trisomy 18 (Edwards' syndrome, a lethal chromosomal aberration, is the second most common autosomal trisomy with an incidence 1: 8000. The aim of this study is to evaluate the sonographic findings in fetuses with trisomy 18. In ten years period (2002-2012 we analyzed fetal blood samples for chromosome abnormalities. Samples were taken by cordocentesis and processed using standard techniques. Sixteen metaphase cells were analyzed for chromosomal constitution in each sample after tripsin-Giemsa banding. A retrospective review of the cytogenetic laboratory database identified all cases of trisomy 18 in ten years period. The prenatal sonographic studies in fetuses at 16 to 22 weeks' gestation, done before invasive testing for the karyotype were reviewed for anatomic findings. From 2100 samples of fetal blood analyzed for chromosomal abnormalities, there were 16 (0,8% with complete trisomy 18. We found no mosaicism, or partial trisomy 18. The women that carried fetuses with trisomy 18 were 17 to 42 years of age. Four of them were above 35. From 16 fetuses with trisomy 18, 14 (87,5% had some anomaly detected by ultrasound, and other two were tested because of advanced maternal age. The most common findings in trisomy 18 were intrauterine growth retardation, polyhidramnios and anomalies of central nervous system, in 29% respectively. Multiple anomalies, including central nervous system, hart and gastrointestinal system anomalies, were also frequent (21%. Therapeutic termination of pregnancy was done in all cases after genetic counseling. Screening for chromosomal abnormalities using ultrasound is at utmost importance in cases of nonhereditary aberrations. Detailed ultrasonographic examinations of fetuses will enable health care providers to form the appropriate management plan for each patient.

  12. Skin manifestations in a case of trisomy 16 mosaicism

    DEFF Research Database (Denmark)

    Ousager, Lilian Bomme; Brandrup, Flemming; Andersen, Charlotte Brasch;

    2006-01-01

    We present a 48-year-old man with unilateral dermatological manifestations including hypertrichosis, telangiectasia, hyperkeratosis and hyperpigmentation. Additional findings included skeletal abnormalities and left-sided hearing loss. Skin biopsies showed changes characteristic of porokeratosis........ Fibroblast karyotyping from affected skin demonstrated trisomy 16 mosaicism, in contrast to the normal karyotype in unaffected skin and blood lymphocytes. The possible role of trisomy 16 in porokeratosis is discussed....

  13. Trisomy 9: Review and report of two new cases

    Energy Technology Data Exchange (ETDEWEB)

    Arnold, G.L.; Kirby, R.S.; Stern, T.P. [Univ. of Arkansas, Little Rock, AR (United States)] [and others

    1995-04-10

    Trisomy 9 is a relatively uncommon chromosome abnormality that may sometimes be seen in the nonmosaic state. We reviewed 23 mosaic and 15 nonmosaic cases of trisomy 9, including 2 new cases, in order to better define the prognosis and phenotype of this disorder. A recognizable trisomy 9 phenotype was identified and included a {open_quotes}bulbous{close_quotes} nose, microphthalmia, and dislocated limbs. Other nonspecific anomalies involving various organ systems were also common. With one exception, all survivors had severe mental impairment. Mosaicism for trisomy 9 predicted longer survival, but the degree of mosaicism in lymphocytes or fibroblasts did not predict survival or degree of impairment. Parental chromosome variations were not uncommon. In contrast to prior reports, no specific prognostic finding was identified. A meiotic origin with loss of a trisomic cell line in mosaic cases is suggested. 43 refs., 2 figs., 2 tabs.

  14. Trisomy 3 may predict a poor response of gastric MALT lymphoma to Helicobacter pylori eradication therapy

    Institute of Scientific and Technical Information of China (English)

    Sawako Taji; Masuji Morita; Masafumi Taniwaki; Kenichi Nomura; Yosuke Matsumoto; Hideaki Sakabe; Naohisa Yoshida; Shoji Mitsufuji; Kazuhiro Nishida; Shigeo Horiike; Shigeo Nakamura

    2005-01-01

    AIM: To investigate the relation of the response to Helicobacter pylori eradication therapy to the depth of tumor invasion and chromosome abnormalities in patients with mucosaassociated lymphoid tissue (MALT) lymphoma and to determine the clinical value of aneuploidy.METHODS: We studied 13 patients with localized gastric MALT lymphoma of stage E1. Before eradication therapy,the depth of tumor invasion was assessed by endoscopic ultrasonography in 8 patients and by endoscopic examination and gastrointestinal series in the remaining patients. To detect chromosomal abnormalities, paraffin-embedded tissue sections of diagnostic biopsy specimens underwent tissuefluorescence in situ hybridization (FISH), using chromosomespecific α-satellite DNA probes for chromosomes 3,7,12,and 18 and YAC clones for t(11;18)(q21;q21).RESULTS: Seven of the 13 patients had complete regression(CR) in response to H pylori eradication therapy. No patient with CR had submucosal tumor invasion. Trisomy 18 was seen in 1 patient with CR, and both trisomies 12 and 18 were present in another patient with CR. All patients with no response or progressive disease had deep submucosal tumor invasion and showed t(11;18)(q21;q21) or trisomy 3. Trisomy 7 was not detected in this series of patients.CONCLUSION: The depth of tumor invasion is an accurate predictor of the response of stage E1 MALT lymphoma to H pylori eradication therapy and is closely associated with the presence of chromosomal abnormalities. Trisomy 3 may predict the aggressive development of MALT lymphoma.

  15. Non-invasive prenatal testing for trisomies 21, 18 and 13

    DEFF Research Database (Denmark)

    Gao, Y.; Jiang, F.; Fu, M.;

    2015-01-01

    OBJECTIVES: To report the clinical performance of massively parallel sequencing-based non-invasive prenatal testing (NIPT) in detecting trisomies 21, 18 and 13 in over 140 000 clinical samples and to compare its performance in low-risk and high-risk pregnancies. METHODS: Between 1 January 2012...... and 31 August 2013, 147 314 NIPT requests to screen for fetal trisomies 21, 18 and 13 using low-coverage whole-genome sequencing of plasma cell-free DNA were received. The results were validated by karyotyping or follow-up of clinical outcomes. RESULTS: NIPT was performed and results obtained in 146 958...... samples, for which outcome data were available in 112 669 (76.7%). Repeat blood sampling was required in 3213 cases and 145 had test failure. Aneuploidy was confirmed in 720/781 cases positive for trisomy 21, 167/218 cases positive for trisomy 18 and 22/67 cases positive for trisomy 13 on NIPT. Nine false...

  16. Sonographic Findings in Partial Type of Trisomy 18

    Directory of Open Access Journals (Sweden)

    Maryam Niknejadi

    2014-01-01

    Full Text Available Trisomy 18 (Edwards syndrome is the second most common trisomy among live born fetuses, with poor prognosis. Estimate of its incidence is between 1 in 4000- 16000 live births. Most of the chromosomal abnormalities in fetuses are detected by prenatal ultrasound findings in the first and second trimesters. In this case report, we present a partial type of trisomy 18 occurring through de novo unbalanced translocation of chromosomes 18 and 21. The ultrasound features enabling the early detection of trisomy 18 include a delayed ossification of calvarium combined with early onset of fetal growth restriction (FGR and the absence of nasal bone through performing triple test followed by amniocentesis. Finally, the parents decided to terminate the pregnancy.

  17. Age-related aneuploidy through cohesion exhaustion

    OpenAIRE

    Jessberger, Rolf

    2012-01-01

    Pregnancy in older women is problematic, as oocytes are particularly prone to chromosome missegregation, and aneuploidy increases with age. Sister chromatid cohesion is weakened or lost with age, having a major impact in age-dependent aneuploidy, as discussed here.

  18. Maternal serum protein profile and immune response protein subunits as markers for non-invasive prenatal diagnosis of trisomy 21, 18, and 13

    KAUST Repository

    Narasimhan, Kothandaraman

    2013-02-01

    Objectives: To use proteomics to identify and characterize proteins in maternal serum from patients at high-risk for fetal trisomy 21, trisomy 18, and trisomy 13 on the basis of ultrasound and maternal serum triple tests. Methods: We performed a comprehensive proteomic analysis on 23 trisomy cases and 85 normal cases during the early second trimester of pregnancy. Protein profiling along with conventional sodium dodecyl sulfate polyacrylamide gel electrophoresis/Tandem mass spectrometry analysis was carried out to characterize proteins associated with each trisomy condition and later validated using Western blot. Results: Protein profiling approach using surface enhanced laser desorption/ionization time-of-flight mass (SELDI-TOF/MS) spectrometry resulted in the identification of 37 unique hydrophobic proteomic features for three trisomy conditions. Using sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by Matrix Assisted Laser Desorption Ionization - Time of Flight/Time of Flight (MALDI-TOF/TOF) and western blot, glyco proteins such as alpha-1-antitrypsin, apolipoprotein E, apolipoprotein H, and serum carrier protein transthyretin were identified as potential maternal serum markers for fetal trisomy condition. The identified proteins showed differential expression at the subunit level. Conclusions: Maternal serum protein profiling using proteomics may allow non-invasive diagnostic testing for the most common trisomies and may complement ultrasound-based methods to more accurately determine pregnancies with fetal aneuploidies. © 2013 John Wiley & Sons, Ltd.

  19. A review of trisomy X (47,XXX

    Directory of Open Access Journals (Sweden)

    Sutherland Ashley

    2010-05-01

    Full Text Available Abstract Trisomy X is a sex chromosome anomaly with a variable phenotype caused by the presence of an extra X chromosome in females (47,XXX instead of 46,XX. It is the most common female chromosomal abnormality, occurring in approximately 1 in 1,000 female births. As some individuals are only mildly affected or asymptomatic, it is estimated that only 10% of individuals with trisomy X are actually diagnosed. The most common physical features include tall stature, epicanthal folds, hypotonia and clinodactyly. Seizures, renal and genitourinary abnormalities, and premature ovarian failure (POF can also be associated findings. Children with trisomy X have higher rates of motor and speech delays, with an increased risk of cognitive deficits and learning disabilities in the school-age years. Psychological features including attention deficits, mood disorders (anxiety and depression, and other psychological disorders are also more common than in the general population. Trisomy X most commonly occurs as a result of nondisjunction during meiosis, although postzygotic nondisjunction occurs in approximately 20% of cases. The risk of trisomy X increases with advanced maternal age. The phenotype in trisomy X is hypothesized to result from overexpression of genes that escape X-inactivation, but genotype-phenotype relationships remain to be defined. Diagnosis during the prenatal period by amniocentesis or chorionic villi sampling is common. Indications for postnatal diagnoses most commonly include developmental delays or hypotonia, learning disabilities, emotional or behavioral difficulties, or POF. Differential diagnosis prior to definitive karyotype results includes fragile X, tetrasomy X, pentasomy X, and Turner syndrome mosaicism. Genetic counseling is recommended. Patients diagnosed in the prenatal period should be followed closely for developmental delays so that early intervention therapies can be implemented as needed. School-age children and

  20. A review of trisomy X (47,XXX).

    Science.gov (United States)

    Tartaglia, Nicole R; Howell, Susan; Sutherland, Ashley; Wilson, Rebecca; Wilson, Lennie

    2010-05-11

    Trisomy X is a sex chromosome anomaly with a variable phenotype caused by the presence of an extra X chromosome in females (47,XXX instead of 46,XX). It is the most common female chromosomal abnormality, occurring in approximately 1 in 1,000 female births. As some individuals are only mildly affected or asymptomatic, it is estimated that only 10% of individuals with trisomy X are actually diagnosed. The most common physical features include tall stature, epicanthal folds, hypotonia and clinodactyly. Seizures, renal and genitourinary abnormalities, and premature ovarian failure (POF) can also be associated findings. Children with trisomy X have higher rates of motor and speech delays, with an increased risk of cognitive deficits and learning disabilities in the school-age years. Psychological features including attention deficits, mood disorders (anxiety and depression), and other psychological disorders are also more common than in the general population. Trisomy X most commonly occurs as a result of nondisjunction during meiosis, although postzygotic nondisjunction occurs in approximately 20% of cases. The risk of trisomy X increases with advanced maternal age. The phenotype in trisomy X is hypothesized to result from overexpression of genes that escape X-inactivation, but genotype-phenotype relationships remain to be defined. Diagnosis during the prenatal period by amniocentesis or chorionic villi sampling is common. Indications for postnatal diagnoses most commonly include developmental delays or hypotonia, learning disabilities, emotional or behavioral difficulties, or POF. Differential diagnosis prior to definitive karyotype results includes fragile X, tetrasomy X, pentasomy X, and Turner syndrome mosaicism. Genetic counseling is recommended. Patients diagnosed in the prenatal period should be followed closely for developmental delays so that early intervention therapies can be implemented as needed. School-age children and adolescents benefit from a

  1. Aneuploidy and proteotoxic stress in cancer

    OpenAIRE

    Donnelly, N; Storchova, Z.

    2015-01-01

    Although nearly ubiquitous in cancer, aneuploidy exerts detrimental effects on human cells. We recently demonstrated that aneuploid human cells exhibit impaired heat shock factor protein 1 (HSF1) and HSP90 function, suggesting a functional link between two recurring features of cancer cells: aneuploidy and proteotoxic stress. Further, our fi ndings implicate HSF1 as a key factor in mitigating the effects of aneuploidy

  2. Frequency of aneuploidy related to age in porcine oocytes.

    Directory of Open Access Journals (Sweden)

    Miroslav Hornak

    Full Text Available It is generally accepted that mammalian oocytes are frequently suffering from chromosome segregation errors during meiosis I, which have severe consequences, including pregnancy loss, developmental disorders and mental retardation. In a search for physiologically more relevant model than rodent oocytes to study this phenomenon, we have employed comparative genomic hybridization (CGH, combined with whole genome amplification (WGA, to study the frequency of aneuploidy in porcine oocytes, including rare cells obtained from aged animals. Using this method, we were able to analyze segregation pattern of each individual chromosome during meiosis I. In contrast to the previous reports where conventional methods, such as chromosome spreads or FISH, were used to estimate frequency of aneuploidy, our results presented here show, that the frequency of this phenomenon was overestimated in porcine oocytes. Surprisingly, despite the results from human and mouse showing an increase in the frequency of aneuploidy with advanced maternal age, our results obtained by the most accurate method currently available for scoring the aneuploidy in oocytes indicated no increase in the frequency of aneuploidy even in oocytes from animals, whose age was close to the life expectancy of the breed.

  3. Frequency of aneuploidy related to age in porcine oocytes.

    Science.gov (United States)

    Hornak, Miroslav; Jeseta, Michal; Musilova, Petra; Pavlok, Antonin; Kubelka, Michal; Motlik, Jan; Rubes, Jiri; Anger, Martin

    2011-04-27

    It is generally accepted that mammalian oocytes are frequently suffering from chromosome segregation errors during meiosis I, which have severe consequences, including pregnancy loss, developmental disorders and mental retardation. In a search for physiologically more relevant model than rodent oocytes to study this phenomenon, we have employed comparative genomic hybridization (CGH), combined with whole genome amplification (WGA), to study the frequency of aneuploidy in porcine oocytes, including rare cells obtained from aged animals. Using this method, we were able to analyze segregation pattern of each individual chromosome during meiosis I. In contrast to the previous reports where conventional methods, such as chromosome spreads or FISH, were used to estimate frequency of aneuploidy, our results presented here show, that the frequency of this phenomenon was overestimated in porcine oocytes. Surprisingly, despite the results from human and mouse showing an increase in the frequency of aneuploidy with advanced maternal age, our results obtained by the most accurate method currently available for scoring the aneuploidy in oocytes indicated no increase in the frequency of aneuploidy even in oocytes from animals, whose age was close to the life expectancy of the breed.

  4. Aneuploidy impairs hematopoietic stem cell fitness and is selected against in regenerating tissues in vivo.

    Science.gov (United States)

    Pfau, Sarah J; Silberman, Rebecca E; Knouse, Kristin A; Amon, Angelika

    2016-06-15

    Aneuploidy, an imbalanced karyotype, is a widely observed feature of cancer cells that has long been hypothesized to promote tumorigenesis. Here we evaluate the fitness of cells with constitutional trisomy or chromosomal instability (CIN) in vivo using hematopoietic reconstitution experiments. We did not observe cancer but instead found that aneuploid hematopoietic stem cells (HSCs) exhibit decreased fitness. This reduced fitness is due at least in part to the decreased proliferative potential of aneuploid hematopoietic cells. Analyses of mice with CIN caused by a hypomorphic mutation in the gene Bub1b further support the finding that aneuploidy impairs cell proliferation in vivo. Whereas nonregenerating adult tissues are highly aneuploid in these mice, HSCs and other regenerative adult tissues are largely euploid. These findings indicate that, in vivo, mechanisms exist to select against aneuploid cells.

  5. Aneuploidy impairs hematopoietic stem cell fitness and is selected against in regenerating tissues in vivo.

    Science.gov (United States)

    Pfau, Sarah J; Silberman, Rebecca E; Knouse, Kristin A; Amon, Angelika

    2016-06-15

    Aneuploidy, an imbalanced karyotype, is a widely observed feature of cancer cells that has long been hypothesized to promote tumorigenesis. Here we evaluate the fitness of cells with constitutional trisomy or chromosomal instability (CIN) in vivo using hematopoietic reconstitution experiments. We did not observe cancer but instead found that aneuploid hematopoietic stem cells (HSCs) exhibit decreased fitness. This reduced fitness is due at least in part to the decreased proliferative potential of aneuploid hematopoietic cells. Analyses of mice with CIN caused by a hypomorphic mutation in the gene Bub1b further support the finding that aneuploidy impairs cell proliferation in vivo. Whereas nonregenerating adult tissues are highly aneuploid in these mice, HSCs and other regenerative adult tissues are largely euploid. These findings indicate that, in vivo, mechanisms exist to select against aneuploid cells. PMID:27313317

  6. Histogenesis of retinal dysplasia in trisomy 13

    OpenAIRE

    Gonzalez-Fernandez Federico; Heffner Reid; Lakshminrusimha Satyan; Chan Ada

    2007-01-01

    Abstract Background Although often associated with holoprosencephaly, little detail of the histopathology of cyclopia is available. Here, we describe the ocular findings in a case of trisomy 13 to better understand the histogenesis of the rosettes, or tubules, characteristic of the retinal dysplasia associated with this condition. Methods A full pediatric autopsy was performed of a near term infant who died shortly after birth from multiple congenital anomalies including fused facial-midline ...

  7. Transcriptional Consequence and Impaired Gametogenesis with High-Grade Aneuploidy in Arabidopsis thaliana

    OpenAIRE

    Kuan-Lin Lo; Long-Chi Wang; I-Ju Chen; Yu-Chen Liu; Mei-Chu Chung; Wan-Sheng Lo

    2014-01-01

    Aneuploidy features a numerical chromosome variant that the number of chromosomes in the nucleus of a cell is not an exact multiple of the haploid number, which may have an impact on morphology and gene expression. Here we report a tertiary trisomy uncovered by characterizing a T-DNA insertion mutant (aur2-1/+) in the Arabidopsis (Arabidopsis thaliana) AURORA2 locus. Whole-genome analysis with DNA tiling arrays revealed a chromosomal translocation linked to the aur2-1 allele, which collective...

  8. Aneuploidy among androgenic progeny of hexaploid triticale (XTriticosecale Wittmack).

    Science.gov (United States)

    Oleszczuk, Sylwia; Rabiza-Swider, Julita; Zimny, Janusz; Lukaszewski, Adam J

    2011-04-01

    Doubled haploids are an established tool in plant breeding and research. Of several methods for their production, androgenesis is technically simple and can efficiently produce substantial numbers of lines. It is well suited to such crops as hexaploid triticale. Owing to meiotic irregularities of triticale hybrids, aneuploidy may affect the efficiency of androgenesis more severely than in meiotically stable crops. This study addresses the issue of aneuploidy among androgenic regenerants of triticale. Plant morphology, seed set and seed quality were better predictors of aneuploidy, as determined cytologically, than flow cytometry. Most aneuploids were hypoploids and these included nullisomics, telosomics, and translocation lines; among 42 chromosome plants were nulli-tetrasomics. Rye chromosomes involved in aneuploidy greatly outnumbered wheat chromosomes; in C(0) rye chromosomes 2R and 5R were most frequently involved. While the frequency of nullisomy 2R was fairly constant in most cross combinations, nullisomy 5R was more frequent in the most recalcitrant combination, and its frequency increased with time spent in culture with up to 70% of green plants recovered late being nullisomic 5R. Given that 5R was not involved in meiotic aberrations with an above-average frequency, it is possible that its absence promotes androgenesis or green plant regeneration. Overall, aneuploidy among tested combinations reduced the average efficiency of double haploid production by 35% and by 69% in one recalcitrant combination, seriously reducing the yield of useful lines. PMID:21170716

  9. Morphological classification of nuchal skin in human fetuses with trisomy 21, 18, and 13 at 12-18 weeks and in a trisomy 16 mouse.

    Science.gov (United States)

    von Kaisenberg, C S; Krenn, V; Ludwig, M; Nicolaides, K H; Brand-Saberi, B

    1998-02-01

    An increase in the nuchal translucency that can be detected at 10-14 weeks of gestation by ultrasound forms the basis for a screening test for chromosomal abnormality. Several mechanisms leading to this increase in skin thickness have been proposed, including changes of the extracellular matrix, cardiac defects and abnormalities of the large vessels. This study examines the composition of the extracellular matrix of the skin in gestational age-matched fetuses with trisomy 21, 18 and 13 from 12-18 weeks. Immunohistochemistry was applied with monoclonal and polyclonal antibodies against collagen type I, III, IV, V and VI and against laminin and fibronectin. Collagen type VI gene expression was further studied by in situ hybridization to detect differences in expression patterns of COL6A1, COL6A3 and COL1A1 between normal fetuses and those with trisomy 21. The ultrastructure of tissue samples was studied by transmission electron microscopy (TEM) and additionally by immunogold TEM. Further, we examined the morphology of the skin in an animal model for Down's syndrome, the murine trisomy 16, by light and TEM. The dermis of trisomy 21 fetuses was richer in collagen type VI than that of normal fetuses and other trisomies, and COL6A1, located on chromosome 21, was expressed in a wider area than COL6A3, which is located on chromosome 2. Collagen type I was less abundant in the skin of trisomy 18 fetuses, while the skin of all three trisomies contained a dense network of collagen type III and V in comparison with normal fetuses. Collagen type IV, of which two genes are located on chromosome 13, was expressed in the basement membranes of the skin in all fetuses and additionally in the dermal fibroblasts only of trisomy 13 fetuses. Likewise, laminin was present in all basement membranes of normal and trisomic fetuses as well as in dermal fibroblasts of fetuses with trisomy 18. LAMA1 and LAMA3 genes are located on chromosome 18. Dermal cysts were found in the skin of trisomy 18

  10. The usage and current approaches of cell free fetal DNA (cffDNA) as a prenatal diagnostic method in fetal aneuploidy screening

    OpenAIRE

    Hülya Erbaba; Gül Pınar

    2015-01-01

    Prenatal diagnosis of invasive and noninvasive tests can be done in a way (NIPT), but because of the invasive methods have risks of infection and abortion, diagnosing non-invasive procedure increasing day by day. One of the widespread cell free fetal DNA in maternal blood test (cffDNA) that is increasing in clinical use has been drawing attention. The incidence of aneuploidy chromosomal anomaly of the kind in which all live births; Trisomy 21 (Down Syndrome) 1/800, trisomy 13 (Patau syndrome)...

  11. Molecular diagnosis of sex chromosome aneuploidy using quantitative PCR.

    Science.gov (United States)

    Mutter, G L; Pomponio, R J

    1991-08-11

    Numeric sex chromosome imbalances, or aneuploidies, are present in several pathological conditions including tumors, abnormal gestations, and clinical syndromes. Here we report a method to identify karyotypic imbalances of the X and Y chromosomes using the polymerase chain reaction (PCR). The polymerase chain reaction was used to quantitatively coamplify the sex chromosome linked genes ZFX and ZFY. Quantitation was facilitated by 1) use of a single primer set which recognizes both templates, 2) incorporation of radiolabelled nucleotides during amplification, and 3) use of amplification conditions which minimize heteroduplex formation. High accuracy of the method was confirmed by concordance with values expected from titrated male and female DNAs and cells from patients with sex chromosome aneuploidy. This approach provides a rapid and reproducible method of evaluating relative abundance of allelic genes, and might be applied to detection of autosomal aneuploidy.

  12. Natural and artefactual aneuploidy in human lymphocytes in extreme old age.

    Science.gov (United States)

    Lezhava, T; Khmaladze, E; Lokhadze, T; Buadze, T

    2008-04-01

    At present it is generally believed that aging is accompanied by an increase in the numbers of cells with altered chromosome sets. However, the problem of aneuploidy in extreme old age (80 years and over) has hardly been subjected to systematic investigation. The purpose of this study was to examine quantitative chromosome changes and relationship between "artefactual" and "natural" aneuploidy in subjects from 80 to 114 years of age using karyotype analyses. Chromosomes were studied in 1136 karyotypes of relatively round metaphases from 40 lymphocyte cultures obtained from 40 apparently normal subjects aged from 80 to 114 ( including 26 men and 14 women). 964 karyotypes from 48 donors aged 20 to 48 served as control. Lymphocytes were cultivation by modification method (Lezhava, 2006). It is suggested that the probability of natural aneuploidy rises substantially among elderly women; while that of artefactual aneuploidy is increased among elderly men; the problem of natural aneuploidy in males remains unclear.

  13. Prenatal screening for fetal aneuploidies with cell-free DNA in the general pregnancy population: a cost-effectiveness analysis

    Science.gov (United States)

    Fairbrother, Genevieve; Burigo, John; Sharon, Thomas; Song, Ken

    2016-01-01

    Abstract Objective: To estimate the cost-effectiveness of fetal aneuploidy screening in the general pregnancy population using non-invasive prenatal testing (NIPT) as compared to first trimester combined screening (FTS) with serum markers and NT ultrasound. Methods: Using a decision-analytic model, we estimated the number of fetal T21, T18, and T13 cases identified prenatally, the number of invasive procedures performed, corresponding normal fetus losses, and costs of screening using FTS or NIPT with cell-free DNA (cfDNA). Modeling was based on a 4 million pregnant women cohort, which represents annual births in the U.S. Results: For the general pregnancy population, NIPT identified 15% more trisomy cases, reduced invasive procedures by 88%, and reduced iatrogenic fetal loss by 94% as compared to FTS. The cost per trisomy case identified with FTS was $497 909. At a NIPT unit, cost of $453 and below, there were cost savings as compared to FTS. Accounting for additional trisomy cases identified by NIPT, a NIPT unit cost of $665 provided the same per trisomy cost as that of FTS. Conclusions: NIPT in the general pregnancy population leads to more prenatal identification of fetal trisomy cases as compared to FTS and is more economical at a NIPT unit cost of $453. PMID:26000626

  14. Coincidence of Trisomy 18 and Robertsonian (13; 14

    Directory of Open Access Journals (Sweden)

    A Alavi

    2012-07-01

    Full Text Available This case report presents a coincidence of trisomy 18 and balanced Robertsonian translocation (13;14. Aneuploidy was suspected based on anomalies detected in ultrasound scan and confirmed with karyotype. In a 31 years-old healthy woman with a history of one miscarriage, second trimester ultrasound scan reported IUGR (<3rd percentile with normal amniotic fluid, bilateral choroid plexus cysts, suspicious agenesis of corpus callosum and clenched hands. Amniocentesis was performed and karyotype was 46xx,der(13;14 (q10;q10,+18. Maternal karyotype was 45xx,der(13;14(q10;q10. Pregnancy was continued due to legal limitation for termination after 20 weeks gestation. Delivery was done at 36 weeks gestation. A female newborn was borned and a physical feature was hypotonia, small mouth, prominent occiput, low-set and posteriorly rotated ears, clenched hands with overlapping fingers and rocker bottom feet. Ultrasound scan and echocardiography detected agenesis of corpus callosum and VSD, ASD, PDA and cardiomegaly. These features are typical of trisomy 18. Balanced Robertsonian translocation usually has no phenotypic expression. Genetic counseling and prenatal diagnosis for future pregnancy was recommended.

  15. Correction of Down syndrome and Edwards syndrome aneuploidies in human cell cultures.

    Science.gov (United States)

    Amano, Tomokazu; Jeffries, Emiko; Amano, Misa; Ko, Akihiro C; Yu, Hong; Ko, Minoru S H

    2015-10-01

    Aneuploidy, an abnormal number of chromosomes, has previously been considered irremediable. Here, we report findings that euploid cells increased among cultured aneuploid cells after exposure to the protein ZSCAN4, encoded by a mammalian-specific gene that is ordinarily expressed in preimplantation embryos and occasionally in stem cells. For footprint-free delivery of ZSCAN4 to cells, we developed ZSCAN4 synthetic mRNAs and Sendai virus vectors that encode human ZSCAN4. Applying the ZSCAN4 biologics to established cultures of mouse embryonic stem cells, most of which had become aneuploid and polyploid, dramatically increased the number of euploid cells within a few days. We then tested the biologics on non-immortalized primary human fibroblast cells derived from four individuals with Down syndrome—the most frequent autosomal trisomy of chromosome 21. Within weeks after ZSCAN4 application to the cells in culture, fluorescent in situ hybridization with a chromosome 21-specific probe detected the emergence of up to 24% of cells with only two rather than three copies. High-resolution G-banded chromosomes further showed up to 40% of cells with a normal karyotype. These findings were confirmed by whole-exome sequencing. Similar results were obtained for cells with the trisomy 18 of Edwards syndrome. Thus a direct, efficient correction of aneuploidy in human fibroblast cells seems possible in vitro using human ZSCAN4. PMID:26324424

  16. Differential effect of aneuploidy on the X chromosome and genes with sex-biased expression in Drosophila.

    Science.gov (United States)

    Sun, Lin; Johnson, Adam F; Li, Jilong; Lambdin, Aaron S; Cheng, Jianlin; Birchler, James A

    2013-10-01

    Global analysis of gene expression via RNA sequencing was conducted for trisomics for the left arm of chromosome 2 (2L) and compared with the normal genotype. The predominant response of genes on 2L was dosage compensation in that similar expression occurred in the trisomic compared with the diploid control. However, the male and female trisomic/normal expression ratio distributions for 2L genes differed in that females also showed a strong peak of genes with increased expression and males showed a peak of reduced expression relative to the opposite sex. For genes in other autosomal regions, the predominant response to trisomy was reduced expression to the inverse of the altered chromosomal dosage (2/3), but a minor peak of increased expression in females and further reduced expression in males were also found, illustrating a sexual dimorphism for the response to aneuploidy. Moreover, genes with sex-biased expression as revealed by comparing amounts in normal males and females showed responses of greater magnitude to trisomy 2L, suggesting that the genes involved in dosage-sensitive aneuploid effects also influence sex-biased expression. Each autosomal chromosome arm responded to 2L trisomy similarly, but the ratio distributions for X-linked genes were distinct in both sexes, illustrating an X chromosome-specific response to aneuploidy.

  17. A tumor profile in Edwards syndrome (trisomy 18).

    Science.gov (United States)

    Satgé, Daniel; Nishi, Motoi; Sirvent, Nicolas; Vekemans, Michel

    2016-09-01

    Constitutional trisomy 18 causes Edwards syndrome, which is characterized by intellectual disability and a particular set of malformations. Although this condition carries high mortality during prenatal and early postnatal life, some of the rare infants who survive the first months develop benign and malignant tumors. To determine the tumor profile associated with Edwards syndrome, we performed a systematic review of the literature. This review reveals a tumor profile differing from those of Down (trisomy 21) and Patau (trisomy 13) syndromes. The literature covers 45 malignancies: 29 were liver cancers, mainly hepatoblastomas found in Japanese females; 13 were kidney tumors, predominantly nephroblastomas; 1 was neuroblastoma; 1 was a Hodgkin disease; and 1 was acute myeloid leukemia in an infant with both trisomy 18 and type 1 neurofibromatosis. No instances of the most frequent malignancies of early life-cerebral tumors, germ cell tumors, or leukemia--are reported in children with pure trisomy 18. Tumor occurrence does not appear to correlate with body weight, tissue growth, or cancer genes mapping to chromosome 18. Importantly, the most recent clinical histories report successful treatment; this raises ethical concerns about cancer treatment in infants with Edwards syndrome. In conclusion, knowledge of the Edwards' syndrome tumor profile will enable better clinical surveillance in at-risk organs (i.e., liver, kidney). This knowledge also provides clues to understanding oncogenesis, including the probably reduced frequency of some neoplasms in infants and children with this genetic condition. © 2016 Wiley Periodicals, Inc. PMID:27474103

  18. SNP-based Microdeletion and Aneuploidy RegisTry (SMART)

    Science.gov (United States)

    2016-04-19

    22q11 Deletion Syndrome; DiGeorge Syndrome; Trisomy 21; Trisomy 18; Trisomy 13; Monosomy X; Sex Chromosome Abnormalities; Cri-du-Chat Syndrome; Angelman Syndrome; Prader-Willi Syndrome; 1p36 Deletion Syndrome

  19. A rare case of chronic myeloid leukemia with secondary chromosomal changes including partial trisomy 17q21 to 17qter and partial monosomy of 16p13.3

    Directory of Open Access Journals (Sweden)

    Mkrtchyan Hasmik

    2010-03-01

    Full Text Available Abstract Background The so-called Philadelphia (Ph chromosome is present in almost all cases with chronic myeloid leukemia (CML. Around 5-10% of these patients show complex translocations involving other chromosomes in addition to and/or besides chromosomes 9 and 22. As nowadays most CML cases are treated with Imatinib, variant rearrangements have in general no specific prognostic significance, though events of therapy resistance remain to be studied. Results Here we report a Ph chromosome positive patient with hematological typical chronic phase CML. Untypically, an unbalanced complex rearrangement involving chromosomes 16 and 17 leading to a deletion of 16pter and partial trisomy of 17q21 to 17qter, was identified besides a trisomy 8 and an additional Ph chromosome in a part of malignant cells. Conclusion Here a novel and cytogenetically unique case of a Ph chromosome positive CML clinically in chronic phase is reported, having complex secondary chromosomal aberrations. Thus, CML patients with complex chromosomal changes are nonetheless treatable by Imatinib.

  20. Loss of the SUMO protease Ulp2 triggers a specific multichromosome aneuploidy.

    Science.gov (United States)

    Ryu, Hong-Yeoul; Wilson, Nicole R; Mehta, Sameet; Hwang, Soo Seok; Hochstrasser, Mark

    2016-08-15

    Post-translational protein modification by the small ubiquitin-related modifier (SUMO) regulates numerous cellular pathways, including transcription, cell division, and genome maintenance. The SUMO protease Ulp2 modulates many of these SUMO-dependent processes in budding yeast. From whole-genome RNA sequencing (RNA-seq), we unexpectedly discovered that cells lacking Ulp2 display a twofold increase in transcript levels across two particular chromosomes: chromosome I (ChrI) and ChrXII. This is due to the two chromosomes being present at twice their normal copy number. An abnormal number of chromosomes, termed aneuploidy, is usually deleterious. However, development of specific aneuploidies allows rapid adaptation to cellular stresses, and aneuploidy characterizes most human tumors. Extra copies of ChrI and ChrXII appear quickly following loss of active Ulp2 and can be eliminated following reintroduction of ULP2, suggesting that aneuploidy is a reversible adaptive mechanism to counteract loss of the SUMO protease. Importantly, increased dosage of two genes on ChrI-CLN3 and CCR4, encoding a G1-phase cyclin and a subunit of the Ccr4-Not deadenylase complex, respectively-suppresses ulp2Δ aneuploidy, suggesting that increased levels of these genes underlie the aneuploidy induced by Ulp2 loss. Our results reveal a complex aneuploidy mechanism that adapts cells to loss of the SUMO protease Ulp2. PMID:27585592

  1. Double Aneuploidy 48,XXY,+21 Associated with a Congenital Heart Defect in a Neonate.

    Science.gov (United States)

    Shu, X; Zou, C; Shen, Z

    2013-12-01

    A neonate with a double aneuploidy associated with congenital heart defect (CHD) suffered from cyanosis after birth. He had typical features of Down syndrome (DS) including hypertelorism, slightly lowset ears with protruding pinna. Doppler echocardiography indicated complex congenital heart disease with an ostium secundum atrial septal defect, enlarged right ventricle, and mild tricuspid valve regurgitation. Further chromosomal analysis showed a karyotype of 48,XXY,+21: a double aneuploidy of DS and Klinefelter syndrome (KS). Until now, only seven cases of double aneuploidy associated with CHD defect have been reported. PMID:24778570

  2. Aneuploidy: implications for protein homeostasis and disease

    Directory of Open Access Journals (Sweden)

    Ana B. Oromendia

    2014-01-01

    Full Text Available It has long been appreciated that aneuploidy – in which cells possess a karyotype that is not a multiple of the haploid complement – has a substantial impact on human health, but its effects at the subcellular level have only recently become a focus of investigation. Here, we summarize new findings characterizing the impact of aneuploidy on protein quality control. Because aneuploidy has been associated with many diseases, foremost among them being cancer, and has also been linked to aging, we also offer our perspective on whether and how the effects of aneuploidy on protein quality control could contribute to these conditions. We argue that acquiring a deeper understanding of the relationship between aneuploidy, disease and aging could lead to the development of new anti-cancer and anti-aging treatments.

  3. Mosaic double aneuploidy: Down syndrome and XYY

    Directory of Open Access Journals (Sweden)

    Mayur Parihar

    2013-01-01

    Full Text Available Chromosomal abnormalities are seen in nearly 1% of live born infants. We report a 5-year-old boy with the clinical features of Down syndrome, which is the most common human aneuploidy. Cytogenetic analysis showed a mosaicism for a double aneuploidy, Down syndrome and XYY. The karyotype was 47, XY,+21[19]/48, XYY,+21[6]. ish XYY (DXZ1 × 1, DYZ1 × 2. Mosaic double aneuploidies are very rare and features of only one of the aneuploidies may predominate in childhood. Cytogenetic analysis is recommended even if the typical features of a recognized aneuploidy are present so that any associated abnormality may be detected. This will enable early intervention to provide the adequate supportive care and management.

  4. Mosaic double aneuploidy: Down syndrome and XYY.

    Science.gov (United States)

    Parihar, Mayur; Koshy, Beena; Srivastava, Vivi Miriam

    2013-07-01

    Chromosomal abnormalities are seen in nearly 1% of live born infants. We report a 5-year-old boy with the clinical features of Down syndrome, which is the most common human aneuploidy. Cytogenetic analysis showed a mosaicism for a double aneuploidy, Down syndrome and XYY. The karyotype was 47, XY,+21[19]/48, XYY,+21[6]. ish XYY (DXZ1 × 1, DYZ1 × 2). Mosaic double aneuploidies are very rare and features of only one of the aneuploidies may predominate in childhood. Cytogenetic analysis is recommended even if the typical features of a recognized aneuploidy are present so that any associated abnormality may be detected. This will enable early intervention to provide the adequate supportive care and management. PMID:24339550

  5. FAST-SeqS: a simple and efficient method for the detection of aneuploidy by massively parallel sequencing.

    Directory of Open Access Journals (Sweden)

    Isaac Kinde

    Full Text Available Massively parallel sequencing of cell-free, maternal plasma DNA was recently demonstrated to be a safe and effective screening method for fetal chromosomal aneuploidies. Here, we report an improved sequencing method achieving significantly increased throughput and decreased cost by replacing laborious sequencing library preparation steps with PCR employing a single primer pair designed to amplify a discrete subset of repeated regions. Using this approach, samples containing as little as 4% trisomy 21 DNA could be readily distinguished from euploid samples.

  6. Trisomy 18 and trisomy 21 mosaicism in a Down's syndrome patient.

    OpenAIRE

    Thomas, I M; Sayee, R; Shavanthi, L; Sridevi, H

    1994-01-01

    A male child with typical features of Down's syndrome and mosaicism of two trisomic cell lines, trisomy 18 (84%) and trisomy 21 (16%), is reported. Non-disjunction or anaphase lag of chromosomes 18 and 21 could be the cause.

  7. Cognitive and neurological aspects of sex chromosome aneuploidies.

    Science.gov (United States)

    Hong, David S; Reiss, Allan L

    2014-03-01

    Sex chromosome aneuploidies are a common group of disorders that are characterised by an abnormal number of X or Y chromosomes. However, many individuals with these disorders are not diagnosed, despite established groups of core features that include aberrant brain development and function. Clinical presentations often include characteristic profiles of intellectual ability, motor impairments, and rates of neurological and psychiatric disorders that are higher than those of the general population. Advances in genetics and neuroimaging have substantially expanded knowledge of potential mechanisms that underlie these phenotypes, including a putative dose effect of sex chromosome genes on neuroanatomical structures and cognitive abilities. Continuing attention to emerging trends in research of sex chromosome aneuploidies is important for clinicians because it informs appropriate management of these common genetic disorders. Furthermore, improved understanding of underlying neurobiological processes has much potential to elucidate sex-related factors associated with neurological and psychiatric disease in general.

  8. Klinefelter syndrome and other sex chromosomal aneuploidies

    Directory of Open Access Journals (Sweden)

    Graham John M

    2006-10-01

    Full Text Available Abstract The term Klinefelter syndrome (KS describes a group of chromosomal disorder in which there is at least one extra X chromosome to a normal male karyotype, 46,XY. XXY aneuploidy is the most common disorder of sex chromosomes in humans, with prevalence of one in 500 males. Other sex chromosomal aneuploidies have also been described, although they are much less frequent, with 48,XXYY and 48,XXXY being present in 1 per 17,000 to 1 per 50,000 male births. The incidence of 49,XXXXY is 1 per 85,000 to 100,000 male births. In addition, 46,XX males also exist and it is caused by translocation of Y material including sex determining region (SRY to the X chromosome during paternal meiosis. Formal cytogenetic analysis is necessary to make a definite diagnosis, and more obvious differences in physical features tend to be associated with increasing numbers of sex chromosomes. If the diagnosis is not made prenatally, 47,XXY males may present with a variety of subtle clinical signs that are age-related. In infancy, males with 47,XXY may have chromosomal evaluations done for hypospadias, small phallus or cryptorchidism, developmental delay. The school-aged child may present with language delay, learning disabilities, or behavioral problems. The older child or adolescent may be discovered during an endocrine evaluation for delayed or incomplete pubertal development with eunuchoid body habitus, gynecomastia, and small testes. Adults are often evaluated for infertility or breast malignancy. Androgen replacement therapy should begin at puberty, around age 12 years, in increasing dosage sufficient to maintain age appropriate serum concentrations of testosterone, estradiol, follicle stimulating hormone (FSH, and luteinizing hormone (LH. The effects on physical and cognitive development increase with the number of extra Xs, and each extra X is associated with an intelligence quotient (IQ decrease of approximately 15–16 points, with language most affected

  9. Systematic Cellular Disease Models Reveal Synergistic Interaction of Trisomy 21 and GATA1 Mutations in Hematopoietic Abnormalities.

    Science.gov (United States)

    Banno, Kimihiko; Omori, Sayaka; Hirata, Katsuya; Nawa, Nobutoshi; Nakagawa, Natsuki; Nishimura, Ken; Ohtaka, Manami; Nakanishi, Mahito; Sakuma, Tetsushi; Yamamoto, Takashi; Toki, Tsutomu; Ito, Etsuro; Yamamoto, Toshiyuki; Kokubu, Chikara; Takeda, Junji; Taniguchi, Hidetoshi; Arahori, Hitomi; Wada, Kazuko; Kitabatake, Yasuji; Ozono, Keiichi

    2016-05-10

    Chromosomal aneuploidy and specific gene mutations are recognized early hallmarks of many oncogenic processes. However, the net effect of these abnormalities has generally not been explored. We focused on transient myeloproliferative disorder (TMD) in Down syndrome, which is characteristically associated with somatic mutations in GATA1. To better understand functional interplay between trisomy 21 and GATA1 mutations in hematopoiesis, we constructed cellular disease models using human induced pluripotent stem cells (iPSCs) and genome-editing technologies. Comparative analysis of these engineered iPSCs demonstrated that trisomy 21 perturbed hematopoietic development through the enhanced production of early hematopoietic progenitors and the upregulation of mutated GATA1, resulting in the accelerated production of aberrantly differentiated cells. These effects were mediated by dosage alterations of RUNX1, ETS2, and ERG, which are located in a critical 4-Mb region of chromosome 21. Our study provides insight into the genetic synergy that contributes to multi-step leukemogenesis. PMID:27134169

  10. Trisomy 8 syndrome owing to isodicentric 8p chromosomes: regional assignment of a presumptive gene involved in corpus callosum development.

    Science.gov (United States)

    Digilio, M C; Giannotti, A; Floridia, G; Uccellatore, F; Mingarelli, R; Danesino, C; Dallapiccola, B; Zuffardi, O

    1994-01-01

    Two patients with trisomy 8 syndrome owing to an isodicentric 8p;8p chromosome are described. Case 1 had a 46,XX/46,XX,-8,+idic(8)(p23) karyotype while case 2, a male, had the same abnormal karyotype without evidence of mosaicism. In situ hybridisation, performed in case 1, showed that the isochromosome was asymmetrical. Agenesis of the corpus callosum (ACC), which is a feature of trisomy 8 syndrome, was found in both patients. Although ACC is associated with aneuploidies for different chromosomes, a review of published reports indicates that, when associated with chromosome 8, this defect is the result of duplication of a gene located within 8p21-pter. Molecular analysis in one of our patients led us to exclude the distal 23 Mb of 8p from this ACC region. Images PMID:8014974

  11. Aneuploidy, the somatic mutation that makes cancer a species of its own.

    Science.gov (United States)

    Duesberg, P; Rasnick, D

    2000-10-01

    The many complex phenotypes of cancer have all been attributed to "somatic mutation." These phenotypes include anaplasia, autonomous growth, metastasis, abnormal cell morphology, DNA indices ranging from 0.5 to over 2, clonal origin but unstable and non-clonal karyotypes and phenotypes, abnormal centrosome numbers, immortality in vitro and in transplantation, spontaneous progression of malignancy, as well as the exceedingly slow kinetics from carcinogen to carcinogenesis of many months to decades. However, it has yet to be determined whether this mutation is aneuploidy, an abnormal number of chromosomes, or gene mutation. A century ago, Boveri proposed cancer is caused by aneuploidy, because it correlates with cancer and because it generates "pathological" phenotypes in sea urchins. But half a century later, when cancers were found to be non-clonal for aneuploidy, but clonal for somatic gene mutations, this hypothesis was abandoned. As a result aneuploidy is now generally viewed as a consequence, and mutated genes as a cause of cancer although, (1) many carcinogens do not mutate genes, (2) there is no functional proof that mutant genes cause cancer, and (3) mutation is fast but carcinogenesis is exceedingly slow. Intrigued by the enormous mutagenic potential of aneuploidy, we undertook biochemical and biological analyses of aneuploidy and gene mutation, which show that aneuploidy is probably the only mutation that can explain all aspects of carcinogenesis. On this basis we can now offer a coherent two-stage mechanism of carcinogenesis. In stage one, carcinogens cause aneuploidy, either by fragmenting chromosomes or by damaging the spindle apparatus. In stage two, ever new and eventually tumorigenic karyotypes evolve autocatalytically because aneuploidy destabilizes the karyotype, ie. causes genetic instability. Thus, cancer cells derive their unique and complex phenotypes from random chromosome number mutation, a process that is similar to regrouping assembly lines

  12. Nondisjunction studies in trisomy 13

    Energy Technology Data Exchange (ETDEWEB)

    Bugge, M.; Petersen, M.B.; Hallberg, A.

    1994-09-01

    The origin of nondisjunction in trisomy 13 has previously been studied using cytogenetic heteromorphisms and RFLP markers, but it was not possible to determine the origin of the additional chromosome in all cases. We have investigated the parental origin of the additional chromosome in 18 cases of trisomy 13 using the following microsatellites: D13S175, D13S171, D13S155, D13S156, D13S154, D13S173, FLT1, D13S118, D13S120 and D13S71. The 18 cases were 5 prenatal, 12 liveborn and 1 stillborn. The karyotypes were 9 of 47,XX+13, 8 of 47,XY+13 and one of 46,XX,-14+t(13;14). The mean maternal age was 32 years and the mean paternal age was 35 years. In 16 of 18 cases the additional chromosome was of maternal origin. In two cases the markers studied so far were not informative. The addition of more DNA markers will enable the detection of the origin of nondisjunction in all cases and the study of altered recombination associated with nondisjunction, as previously described in trisomy 21 and 47,XXY.

  13. Non-invasive prenatal testing of trisomy 18 by an epigenetic marker in first trimester maternal plasma.

    Directory of Open Access Journals (Sweden)

    Da Eun Lee

    Full Text Available BACKGROUND: Quantification of cell-free fetal DNA by methylation-based DNA discrimination has been used in non-invasive prenatal testing of fetal chromosomal aneuploidy. The maspin (Serpin peptidase inhibitor, clade B (ovalbumin, member 5; SERPINB5 gene, located on chromosome 18q21.33, is hypomethylated in the placenta and completely methylated in maternal blood cells. The objective of this study was to evaluate the accuracy of non-invasive detection of fetal trisomy 18 using the unmethylated-maspin (U-maspin gene as a cell-free fetal DNA marker and the methylated-maspin (M-maspin gene as a cell-free total DNA marker in the first trimester of pregnancy. METHODOLOGY/PRINCIPAL FINDINGS: A nested case-control study was conducted using maternal plasma collected from 66 pregnant women, 11 carrying fetuses with trisomy 18 and 55 carrying normal fetuses. Median U-maspin concentrations were significantly elevated in women with trisomy 18 fetuses compared with controls (27.2 vs. 6.7 copies/mL; P<0.001. Median M-maspin concentrations were also significantly higher in women with trisomy 18 fetuses than in controls (96.9 vs. 19.5 copies/mL, P<0.001. The specificities of U-maspin and M-maspin concentrations for non-invasive fetal trisomy 18 detection were 96.4% and 74.5%, respectively, with a sensitivity of 90.9%. CONCLUSIONS: Our results suggest that U-maspin and M-maspin concentrations may be useful as potential biomarkers for non-invasive detection of fetal trisomy 18 in the first trimester of pregnancy, irrespective of the sex and genetic variations of the fetus.

  14. 应用多重连接依赖探针扩增技术快速检测胎儿染色体非整倍体异常%Application of multiplex ligation-dependent probe amplification for rapid detection of aneuploidies in prenatal diagnosis

    Institute of Scientific and Technical Information of China (English)

    马定远; 许争峰; 胡平; 张菁菁; 易龙; 季修庆; 杨驰; 成建; 李璃; 林颖

    2011-01-01

    Objective To determine the applicability of multiplex ligation-dependent probe amplification (MLPA) for rapid detection of aneuploidies in prenatal diagnosis.Methods A total of 561 prenatal samples were analyzed in parallel by MLPA and traditional karyotyping. Another 20 clinical samples with known common chromosome abnormalities were also determined by MLPA to evaluate the accuracy and reliability of MLPA. The results obtained from MLPA were compared with that from traditional karyotyping.Results The results were available within 48 h.A total of 38 aneuploidies were identified by MLPA,including 20 cases of trisomy 21,10 cases of trisomy 18,1 case of trisomy 13,4 cases of Turner syndrome,1 case of Klinefelter syndrome,1 case of 47,XYY trisomy and 1 case of 48,XYY,+18.MLPA was able to detect all the expected aneuploidies with 100% accuracy.The results obtained from MLPA agreed with traditional karyotyping.Among 561 prenatal samples,the results of 550 samples were concordant with those of karyotyping,and the coincidence rate of MLPA was 98.04%.Conclusion MLPA is a rapid,simple and reliable method for detection of the most common chromosome aneuploidies in prenatal diagnosis.MLPA is a valuable tool in prenatal clinical practice.%目的 探讨多重连接依赖探针扩增(multiplex ligation-dependent probe amplification,MLPA)技术在常见染色体非整倍体异常检测及其在产前诊断中的应用价值.方法 应用MLPA技术检测561份产前诊断样本和20例已知染色体异倍体标本,所有样本均进行常规染色体核型分析,比较MLPA结果和染色体核型分析结果,评价MLPA技术的临床符合率.结果 MLPA技术能够在48 h内出具检测结果,共检测出38例染色体异倍体,包括20例21-三体,10例18-三体,1例13-三体,4例Turner综合征,1例Klinefelter综合征,1例超雄综合征,1例48,XYY,+18双三体综合征.MLPA结果与染色体核型结果一致,检测结果100%准确.在561份产前诊断样本中,有550

  15. Aneuploidy in spermatozoa in infertile men

    OpenAIRE

    Grabar V.V.; Feskov A.M.; Stefanovich A.V.; Zhilkova E.S.

    2014-01-01

    Background. An important problem is to investigate the frequency of aneuploidy in sperms of infertile men according to their changes in karyotype, that would allow to understand the contribution of paternal factor in the formation of chromosomal aberrations of embryos. Objective. To study the frequency of aneuploidy in spermatozoa from infertile men with normal karyotype and chromosomal changes. Methods. Fluorescence in situ hybridization (FISH) of spermatozoa (chromosomes 13, 16, 18, 21, 22,...

  16. The eXtraordinarY Kids Clinic: an interdisciplinary model of care for children and adolescents with sex chromosome aneuploidy

    Directory of Open Access Journals (Sweden)

    Tartaglia N

    2015-07-01

    Full Text Available Nicole Tartaglia,1,2 Susan Howell,1,2 Rebecca Wilson,2 Jennifer Janusz,1,2 Richard Boada,1,2 Sydney Martin,2 Jacqueline B Frazier,2 Michelle Pfeiffer,2 Karen Regan,2 Sarah McSwegin,2 Philip Zeitler1,2 1Department of Pediatrics, University of Colorado School of Medicine, 2Child Development Unit, Children's Hospital Colorado, Aurora, CO, USA Purpose: Individuals with sex chromosome aneuploidies (SCAs are born with an atypical number of X and/or Y chromosomes, and present with a range of medical, developmental, educational, behavioral, and psychological concerns. Rates of SCA diagnoses in infants and children are increasing, and there is a need for specialized interdisciplinary care to address associated risks. The eXtraordinarY Kids Clinic was established to provide comprehensive and experienced care for children and adolescents with SCA, with an interdisciplinary team composed of developmental–behavioral pediatrics, endocrinology, genetic counseling, child psychology, pediatric neuropsychology, speech–language pathology, occupational therapy, nursing, and social work. The clinic model includes an interdisciplinary approach to care, where assessment results by each discipline are integrated to develop unified diagnostic impressions and treatment plans individualized for each patient. Additional objectives of the eXtraordinarY Kids Clinic program include prenatal genetic counseling, research, education, family support, and advocacy. Methods: Satisfaction surveys were distributed to 496 patients, and responses were received from 168 unique patients. Results: Satisfaction with the overall clinic visit was ranked as “very satisfied” in 85%, and as “satisfied” in another 9.8%. Results further demonstrate specific benefits from the clinic experience, the importance of a knowledgeable clinic coordinator, and support the need for similar clinics across the country. Three case examples of the interdisciplinary approach to assessment and

  17. Trisomy 18 syndrome with cleft foot.

    OpenAIRE

    Castle, D; Bernstein, R.

    1988-01-01

    Ectrodactyly of the feet has been reported only twice in association with trisomy 18 syndrome. A severe form of this anomaly, the first with published illustrative x rays, is described in a male infant with trisomy 18 syndrome. It is suggested that this may represent an extreme expression of the foot anomalies more commonly associated with this syndrome.

  18. The usage and current approaches of cell free fetal DNA (cffDNA as a prenatal diagnostic method in fetal aneuploidy screening

    Directory of Open Access Journals (Sweden)

    Hülya Erbaba

    2015-12-01

    Full Text Available Prenatal diagnosis of invasive and noninvasive tests can be done in a way (NIPT, but because of the invasive methods have risks of infection and abortion, diagnosing non-invasive procedure increasing day by day. One of the widespread cell free fetal DNA in maternal blood test (cffDNA that is increasing in clinical use has been drawing attention. The incidence of aneuploidy chromosomal anomaly of the kind in which all live births; Trisomy 21 (Down Syndrome 1/800, trisomy 13 (Patau syndrome 1 /10,000, trisomy 18 (Edwards syndrome is a form of 1/6000. Because of the high mortality and morbidity, it is vital that congenital anomalies should be diagnosed in prenatal period. Aneuploidy testing for high-risk pregnant women after the 10th week of pregnancy in terms of the blood sample is taken and free fetal DNA in maternal plasma is based on the measurement of the relative amount. Knowledge of the current criteria for use by healthcare professionals in the field test will allow the exclusion of maternal and fetal risks. In this study, it is aimed to demonstrate current international approaches related to the positive and negative sides of non-invasive that is one of the prenatal diagnostic methods of cffDNA test. J Clin Exp Invest 2015; 6 (4: 414-417

  19. From pediatric history. Important personalities in relation to some genetic defects - "trisomies".

    Science.gov (United States)

    Brucknerova, Ingrid; Holomanova, Anna; Mach, Mojmir; Ujhazy, Eduard

    2012-01-01

    The aim of this study is to present a short biography of some important physicians and describe the most prominent differences between trisomy 13, 18 and 21. The authors present the most prominent differences between trisomy 13, 18 and 21. The work of many important physicians, geneticists, has helped in the process of recognition of congenital anomalies. This group of famous persons includes Patau, Edwards and Down. PMID:23391875

  20. Clinical value of eatly-mid trimester ultrasound scan in the diagnosis of ehromosomal aneuploidy abnormalities%早中孕产前超声检查在染色体非整倍体异常胎儿中的诊断价值

    Institute of Scientific and Technical Information of China (English)

    陈秋妍; 张茜; 郭红梅; 曾秀梅

    2016-01-01

    目的:探讨早中孕期产前超声检查在染色体非整倍体异常胎儿中的诊断价值。方法对2014年3月~2015年10月在我院经羊水细胞、脐血细胞及绒毛细胞染色体核型分析诊断为非整倍体异常的38例胎儿早中孕期(11~28周)产前超声异常声像图进行总结分析。结果38例羊水细胞染色体核型分析确诊为非整倍体异常的胎儿中超声显示异常32例(84.2%,32/38),包括21-三体17例(17/23)、18-三体11例(11/11)、13-三体2例(2/2),45,X 2例(2/2)。其中单发畸形10例(31.2%,10/32),多发畸形12例(37.6%,12/32),仅表现为超声软指标10例(31.2%,10/32)。18-三体、13-三体、45,X胎儿均有超声结构异常,18-三体胎儿中8例表现为超声结构异常合并软指标异常。21-三体胎儿中10例,仅表现为超声软指标异常,7例表现为超声结构异常合并软指标异常。38例非整倍体异常胎儿中以心脏畸形检出例数居多(31.5%,12/38),而颈部淋巴水囊瘤是45,X胎儿的典型超声表现。结论非整倍体异常胎儿常伴有异常的超声声像图表现,部分还有相应的典型超声畸形谱和超声软指标,早中孕期产前超声检查作为非侵入性检查技术对于非整倍体异常胎儿的诊断有重要价值。%Objective To investigate the clinical application of eatly-mid trimester ultrasound scan in the diagnosis of ehromo-somal aneuploidy abnormalities .Methods Early-mid trimester ultrasound imaging features in 38 aneuploidy abnormal fetuses which were diagnosed by CVS , amniocentesis and umbilical vein puncture in our hospital from April 2014 to Octocber 2015 were analyzed retrospectively .Results 38 cases of aneuploidy abnormalities dectected by CVS , amniocentesis and umbilical vein puncture were examined by prenatal ultrasound .Of these cases, 32 were found abnormalities , including 17 with

  1. Haplotype mapping of a diploid non-meiotic organism using existing and induced aneuploidies.

    Directory of Open Access Journals (Sweden)

    Melanie Legrand

    2008-01-01

    Full Text Available Haplotype maps (HapMaps reveal underlying sequence variation and facilitate the study of recombination and genetic diversity. In general, HapMaps are produced by analysis of Single-Nucleotide Polymorphism (SNP segregation in large numbers of meiotic progeny. Candida albicans, the most common human fungal pathogen, is an obligate diploid that does not appear to undergo meiosis. Thus, standard methods for haplotype mapping cannot be used. We exploited naturally occurring aneuploid strains to determine the haplotypes of the eight chromosome pairs in the C. albicans laboratory strain SC5314 and in a clinical isolate. Comparison of the maps revealed that the clinical strain had undergone a significant amount of genome rearrangement, consisting primarily of crossover or gene conversion recombination events. SNP map haplotyping revealed that insertion and activation of the UAU1 cassette in essential and non-essential genes can result in whole chromosome aneuploidy. UAU1 is often used to construct homozygous deletions of targeted genes in C. albicans; the exact mechanism (trisomy followed by chromosome loss versus gene conversion has not been determined. UAU1 insertion into the essential ORC1 gene resulted in a large proportion of trisomic strains, while gene conversion events predominated when UAU1 was inserted into the non-essential LRO1 gene. Therefore, induced aneuploidies can be used to generate HapMaps, which are essential for analyzing genome alterations and mitotic recombination events in this clonal organism.

  2. Aneuploidy: the impact of chromosome imbalance on nuclear organization and overall genome expression.

    Science.gov (United States)

    Hervé, B; Coussement, A; Gilbert, T; Dumont, F; Jacques, S; Cuisset, L; Chicard, M; Hizem, S; Bourdoncle, P; Letourneur, F; Dupont, C; Vialard, F; Choiset, A; Dupont, J-M

    2016-07-01

    The organization and dynamics of chromatin within the interphase nucleus as chromosome territories (CTs) and the relationship with transcriptional regulation are not fully understood. We studied a natural example of chromosomal disorganization: aneuploidy due to trisomies 13, 18 and 21. We hypothesized that the presence of an extra copy of one chromosome alters the CT distribution, which perturbs transcriptional activity. We used 3D-FISH to study the position of the chromosomes of interest (18 and 21) in cultured amniocytes and chorionic villus cells from pregnancies with a normal or aneuploid karyotype. We studied the volumes of nuclei and CTs in both conditions and performed a compared transcriptome analysis. We did not observe any differences between euploid and aneuploid cells in terms of the radial and relative CT positions, suggesting that the same rules govern nuclear organization in cases of trisomy. We observed lower volumes for CTs 18 and 21. Overall genome expression profiles highlighted changes in the expression of a subset of genes in trisomic chromosomes, while the majority of transcriptional changes concerned genes located on euploid chromosomes. Our results suggest that a dosage imbalance of the genes on trisomic chromosomes is associated with a disturbance of overall genomic expression. PMID:27283765

  3. Noninvasive prenatal diagnosis of fetal trisomy 18 and trisomy 13 by maternal plasma DNA sequencing.

    Directory of Open Access Journals (Sweden)

    Eric Z Chen

    Full Text Available Massively parallel sequencing of DNA molecules in the plasma of pregnant women has been shown to allow accurate and noninvasive prenatal detection of fetal trisomy 21. However, whether the sequencing approach is as accurate for the noninvasive prenatal diagnosis of trisomy 13 and 18 is unclear due to the lack of data from a large sample set. We studied 392 pregnancies, among which 25 involved a trisomy 13 fetus and 37 involved a trisomy 18 fetus, by massively parallel sequencing. By using our previously reported standard z-score approach, we demonstrated that this approach could identify 36.0% and 73.0% of trisomy 13 and 18 at specificities of 92.4% and 97.2%, respectively. We aimed to improve the detection of trisomy 13 and 18 by using a non-repeat-masked reference human genome instead of a repeat-masked one to increase the number of aligned sequence reads for each sample. We then applied a bioinformatics approach to correct GC content bias in the sequencing data. With these measures, we detected all (25 out of 25 trisomy 13 fetuses at a specificity of 98.9% (261 out of 264 non-trisomy 13 cases, and 91.9% (34 out of 37 of the trisomy 18 fetuses at 98.0% specificity (247 out of 252 non-trisomy 18 cases. These data indicate that with appropriate bioinformatics analysis, noninvasive prenatal diagnosis of trisomy 13 and trisomy 18 by maternal plasma DNA sequencing is achievable.

  4. Aneuploidy in spermatozoa in infertile men

    Directory of Open Access Journals (Sweden)

    Grabar V.V.

    2014-09-01

    Full Text Available Background. An important problem is to investigate the frequency of aneuploidy in sperms of infertile men according to their changes in karyotype, that would allow to understand the contribution of paternal factor in the formation of chromosomal aberrations of embryos. Objective. To study the frequency of aneuploidy in spermatozoa from infertile men with normal karyotype and chromosomal changes. Methods. Fluorescence in situ hybridization (FISH of spermatozoa (chromosomes 13, 16, 18, 21, 22, X and Y was performed in 79 infertile men with normal karyotype, in 16 with chromosomal abnormalities, in 18 with chromosomal polymorphism and in 29 healthy men. In total 23,867 of sperm cores were analyzed. Results. In men with infertility an aneuploid sperms were in 5.7 times more often than in fertile patients (P˂0,01. An aneuploidy of sperms in infertile men with a chromosomal abnormality were in 2.1 times, with a chromosomal polymorphism in 1.4 times more often than in infertile patients with a normal karyotype (P˂0,05. In all patients the most common aneuploidies were in chromosomes XY, 21 and 22. The study of aneuploidy frequency in spermatozoa at different variants of chromosomal pathology showed that in men with paracentric inversions rate was 5.75 - 7.65%, whereas in patients with quantitative and other structural chromosomal abnormalities it was above 11.73 - 17.82%. Conclusion. The frequency of chromosomal aberrations in spermatozoa is highest in men with genomic and chromosomal mutations. In infertile patients with changes in the karyotype the gametes with mutations de novo can be produced. Citation: Grabar VV, Feskov AM, Stefanovich AV, Zhilkova ES. [Aneuploidy in spermatozoa in infertile men]. Morpho-logia. 2014;8(3:7-12. Russian.

  5. FISH快速检测自然流产绒毛染色体非整倍体异常的临床价值%Rapid Detection of Chromosomal Aneuploidy in Chorionic Villus of Spontaneous Abortion by Fluorescence in Situ Hybridization

    Institute of Scientific and Technical Information of China (English)

    吴庆华; 史惠蓉; 解艳华; 江淼; 赵振华; 鲁宁; 孔祥东

    2012-01-01

    目的:探讨应用荧光原位杂交技术( FISH)对早期自然流产绒毛染色体非整倍体检测的临床价值.方法:对30例因自然流产行清宫术的绒毛组织行FISH分析,使用7种探针对13、16、18、21、22号和X、Y染色体进行了检测,并对这30例流产夫妇行外周血淋巴细胞染色体常规核型分析.结果:FISH分析的30例自然流产的绒毛组织中,有17例检测出了异常信号,检出率为57%,其中8例16-三体、2例22-三体、2例13-三体和5例三倍体.30例自然流产夫妇外周血淋巴细胞染色体核型未见异常.结论:FISH技术可以快速、简便地检测出流产物绒毛组织染色体非整倍体的异常,FISH技术的应用可以为自然流产夫妇遗传咨询提供重要的信息.%Objective;To evaluate the application of fluorescence in situ hybridization (FISH) for the detection of chromosomal aneuploidy in chorionic villus of spontaneous abortion. Methods:Thirty cases of chori-onic villus were analyzed by FISH, and seven probes were used to detect chromosomes 13, 16, 18, 21, 22, X, Y respectively. Results:In the thirty cases, seventeen cases were shown abnormal signals by FISH with detection rate of 57%, including eight cases of 16-trisomy, two cases of 22-trisomy, two cases of 13-trisomy and five cases of triploidy. Conclusions:FISH analysis is a rapid and easy method in the detection of chromosomal aneuploidy in chorionic villus. The application of FISH can provide important information of genetic counseling for the patients with spontaneous abortion.

  6. Short hard palate in prenatal trisomy 21

    DEFF Research Database (Denmark)

    Lauridsen, H; Hansen, Birgit; Reintoft, I;

    2005-01-01

    Structured Abstract Authors - Lauridsen H, Hansen BF, Reintoft I, Keeling JW, Skovgaard LT, Kjaer I Objective - The aim of the present study was for the first time to examine on postmortal material the total midpalatal length of the hard palate and the length of its two components (the maxillary...... and palatine parts) in trisomy 21 fetuses, and to compare the results to normal standards. Design - Material from 31 human fetuses with genetically verified trisomy 21 was studied. The fetuses were derived from legally induced or spontaneous abortions. Palates were, after sectioning, radiographed in lateral...... of the palatal components in trisomy 21 was compared to normal standards. Results - For CRL 150 mm and CRL 170 mm it appears that all three palatal lengths, total length, maxillary length, and palatinal length are significantly shorter in fetuses with trisomy 21. Conclusion - The main conclusion of our study...

  7. Natural history of trisomy 18 and trisomy 13: II. Psychomotor development

    Energy Technology Data Exchange (ETDEWEB)

    Baty, B.J.; Jorde, L.B.; Blackburn, B.L.; Carey, J.C. [Univ. of Utah School of Medicine, Salt Lake City, UT (United States)

    1994-01-15

    Developmental data were abstracted from medical records on 50 trisomy 18 individuals ranging in age from 1 to 232 months and 12 trisomy 13 individuals ranging in age from 1 to 130 months. Data on the age when trisomy 18 and trisomy 13 children achieved developmental skills were collected from a larger group of 62 trisomy 18 individuals and 14 trisomy 13 individuals whose families filled out parent questionnaires. Developmental quotient (DQ), defined as developmental age divided by chronological age, averaged 0.18 for trisomy 18 and 0.25 for trisomy 13. There was a dramatic drop in DQ from infancy to later childhood. The highest DQs and the greatest variation in DQs were in the first 2-3 years of life. Developmental ages in 7 skill areas were significantly different, with daily living and receptive language having the highest values and motor and communication skills having the lowest. When chronological age was taken into account, there was no significant difference in DQs in the same 7 skill areas, although there was a trend that was similar to the pattern of differences with developmental age. Older children could use a walker, understand words and phrases, use a few words and/or signs, crawl, follow simple commands, recognize and interact with others, and play independently. Walking and some toileting skills were also reported for trisomy 13. Although individual with trisomy 18 and trisomy 13 were clearly functioning in the severe to profound developmentally handicapped range, they did achieve some psychomotor maturation and always continued to learn. 8 refs., 2 figs., 5 tabs.

  8. 高龄孕妇胎儿染色体非整倍体异常的早孕期检测%Detection of fetal chromosomal aneuploidy in pregnant women at advanced maternal age during the first trimester

    Institute of Scientific and Technical Information of China (English)

    汪淑娟; 高志英; 卢彦平; 李亚里; 姜淑芳; 汪龙霞; 张立文

    2014-01-01

    Objective To investigate the value of maternal plasma cell-free fetal DNA (cff-DNA) examination in detection of fetal chromosomal aneuploidy in pregnant women at advanced maternal ages during the first trimester of pregnancy. Methods A total of 136 pregnant women (11 to 13+6 gestational weeks) with advanced maternal ages were screened for fetal chromosomal aneuploidy with ultrasound and maternal plasma cff-DNA examination during March 1, 2011 to August 31, 2013, and the results were then confirmed by karyotype analysis and fluorescence in situ hybridization (FISH). Results Of the 136 women examined, cff-DNA screening detected chromosomal aneuploidy in 5 cases, including trisome-21 in 3 cases, trisome-18 in 1 case, and 45,X in 1 case as confirmed subsequently by karyotype analysis. Ultrasound screening reported a normal finding in one case of trisomy-21, thickening of the NT in the case of trisomy-18, and fetal anasarca in the case of 45,X. Karyotype analysis and follow-up of the women did not find chromosomal abnormality in the 131 negative cases screened by cff-DNA detection. Conclusion Screening of materal plasma cff-DNA allows accurate and early detection of fetal chromosomal aneuploidy in women of advanced maternal ages to avoid unnecessary invasive antenatal examinations.%目的:评价孕妇血浆胎儿游离DNA检测对高龄孕妇胎儿染色体非整倍体异常的早孕期检测价值。方法自2011年3月1日~2013年8月31日,采用早孕期超声筛查和孕妇血浆胎儿游离DNA检测技术,对136例孕11-13+6周的高龄孕妇进行检测,并通过染色体核型分析、荧光染色体原位杂交进行结果验证。结果cff-DNA检测,检出3例21-三体,1例18-三体(同时存在NT增厚),1例45,X(超声提示胎儿全身水肿),与荧光染色体杂交的结果一致,分别为47,XN,+21、47,XN,+18、45,X;筛查阴性者,未发现染色体异常。结论在早孕期开展cff-DNA检测,能更早期、

  9. Sex ratios in fetuses and liveborn infants with autosomal aneuploidy

    Energy Technology Data Exchange (ETDEWEB)

    Heuther, C.A.; Martin, R.L.M.; Stoppelman, S.M. [Univ. of Cincinnati, OH (United States)] [and others

    1996-06-14

    Ten data sources were used substantially to increase the available data for estimating fetal and livebirth sex ratios for Patau (trisomy 13), Edwards (trisomy 18), and Down (trisomy 21) syndromes and controls. The fetal sex ratio estimate was 0.88 (N = 584) for trisomy 13, 0.90 (N = 1702) for trisomy 18, and 1.16 (N = 3154) for trisomy 21. All were significantly different from prenatal controls (1.07). The estimated ratios in prenatal controls were 1.28 (N = 1409) for CVSs and 1.06 (N = 49427) for amniocenteses, indicating a clear differential selection against males, mostly during the first half of fetal development. By contrast, there were no sex ratio differences for any of the trisomies when comparing gestational ages <16 and >16 weeks. The livebirth sex ratio estimate was 0.90 (N = 293) for trisomy 13, 0.63 (N = 497) for trisomy 18, and 1.15 (N = 6424) for trisomy 21, the latter two being statistically different than controls (1.05) (N = 3660707). These ratios for trisomies 13 and 18 were also statistically different than the ratio for trisomy 21. Only in trisomy 18 did the sex ratios in fetuses and livebirths differ, indicating a prenatal selection against males >16 weeks. No effects of maternal age or race were found on these estimates for any of the fetal or livebirth trisomies. Sex ratios for translocations and mosaics were also estimated for these aneuploids. Compared to previous estimates, these results are less extreme, most likely because of larger sample sizes and less sample bias. They support the hypothesis that these trisomy sex ratios are skewed at conception, or become so during embryonic development through differential intrauterine selection. The estimate for Down syndrome livebirths is also consistent with the hypothesis that its higher sex ratio is associated with paternal nondisjunction. 36 refs., 5 tabs.

  10. Maternal Germinal Trisomy 21 in Down Syndrome

    Directory of Open Access Journals (Sweden)

    Maj A. Hultén

    2014-01-01

    Full Text Available It has now been over 50 years since it was discovered that Down syndrome is caused by an extra chromosome 21, i.e., trisomy 21. In the interim, it has become clear that in the majority of cases, the extra chromosome is inherited from the mother, and there is, in this respect, a strong maternal age effect. Numerous investigations have been devoted to clarifying the underlying mechanism, most recently suggesting that this situation is exceedingly complex, involving both biological and environmental factors. On the other hand, it has also been proposed that germinal trisomy 21 mosaicism, arising during the very early stages of maternal oogenesis with accumulation of trisomy 21 germ cells during subsequent development, may be the main predisposing factor. We present data here on the incidence of trisomy 21 mosaicism in a cohort of normal fetal ovarian samples, indicating that an accumulation of trisomy 21 germ cells does indeed take place during fetal oogenesis, i.e., from the first to the second trimester of pregnancy. We presume that this accumulation of trisomy 21 (T21 cells is caused by their delay in maturation and lagging behind the normal cells. We further presume that this trend continues during the third trimester of pregnancy and postnatally, up until ovulation, thereby explaining the maternal age effect in Down syndrome.

  11. Noninvasive prenatal diagnosis of fetal trisomy 18 and trisomy 13 by maternal plasma DNA sequencing.

    NARCIS (Netherlands)

    Chen, E.Z.; Chiu, R.W.; Sun, H.; Akolekar, R.; Chan, K.C.; Leung, T.Y.; Jiang, P.; Zheng, Y.W.; Lun, F.M.; Chan, L.Y.; Jin, Y.; Go, A.T.; Lau, E.T; To, W.W.; Leung, W.C.; Tang, R.Y.; Au-Yeung, S.K.; Lam, H.; Kung, Y.Y.; Zhang, X.; Vugt, J.M.G. van; Minekawa, R.; Tang, M.H.; Wang, J.; Oudejans, C.B.; Lau, T.K.; Nicolaides, K.H.; Lo, Y.M.

    2011-01-01

    Massively parallel sequencing of DNA molecules in the plasma of pregnant women has been shown to allow accurate and noninvasive prenatal detection of fetal trisomy 21. However, whether the sequencing approach is as accurate for the noninvasive prenatal diagnosis of trisomy 13 and 18 is unclear due t

  12. Risk for trisomy 21 in offspring of individuals who have relatives with trisomy 21.

    Science.gov (United States)

    Abuelo, D; Barsel-Bowers, G; Busch, W; Pueschel, S; Pezzullo, J

    1986-10-01

    This study was performed to determine if sibs and other relatives of individuals with trisomy 21 are themselves at increased risk for having offspring with trisomy 21. The results suggest that the reproductive risk to these relatives is not increased beyond the risk to the general population.

  13. False Negative Cell-Free DNA Screening Result in a Newborn with Trisomy 13

    Directory of Open Access Journals (Sweden)

    Yang Cao

    2016-01-01

    Full Text Available Background. Noninvasive prenatal screening (NIPS is revolutionizing prenatal screening as a result of its increased sensitivity, specificity. NIPS analyzes cell-free fetal DNA (cffDNA circulating in maternal plasma to detect fetal chromosome abnormalities. However, cffDNA originates from apoptotic placental trophoblast; therefore cffDNA is not always representative of the fetus. Although the published data for NIPS testing states that the current technique ensures high sensitivity and specificity for aneuploidy detection, false positives are possible due to isolated placental mosaicism, vanishing twin or cotwin demise, and maternal chromosome abnormalities or malignancy. Results. We report a case of false negative cell-free DNA (cfDNA screening due to fetoplacental mosaicism. An infant male with negative cfDNA screening result was born with multiple congenital abnormalities. Postnatal chromosome and FISH studies on a blood specimen revealed trisomy 13 in 20/20 metaphases and 100% interphase nuclei, respectively. FISH analysis on tissues collected after delivery revealed extraembryonic mosaicism. Conclusions. Extraembryonic tissue mosaicism is likely responsible for the false negative cfDNA screening result. This case illustrates that a negative result does not rule out the possibility of a fetus affected with a trisomy, as cffDNA is derived from the placenta and therefore may not accurately represent the fetal genetic information.

  14. False Negative Cell-Free DNA Screening Result in a Newborn with Trisomy 13

    Science.gov (United States)

    Cao, Yang; Hoppman, Nicole L.; Kerr, Sarah E.; Sattler, Christopher A.; Borowski, Kristi S.; Wick, Myra J.; Highsmith, W. Edward; Aypar, Umut

    2016-01-01

    Background. Noninvasive prenatal screening (NIPS) is revolutionizing prenatal screening as a result of its increased sensitivity, specificity. NIPS analyzes cell-free fetal DNA (cffDNA) circulating in maternal plasma to detect fetal chromosome abnormalities. However, cffDNA originates from apoptotic placental trophoblast; therefore cffDNA is not always representative of the fetus. Although the published data for NIPS testing states that the current technique ensures high sensitivity and specificity for aneuploidy detection, false positives are possible due to isolated placental mosaicism, vanishing twin or cotwin demise, and maternal chromosome abnormalities or malignancy. Results. We report a case of false negative cell-free DNA (cfDNA) screening due to fetoplacental mosaicism. An infant male with negative cfDNA screening result was born with multiple congenital abnormalities. Postnatal chromosome and FISH studies on a blood specimen revealed trisomy 13 in 20/20 metaphases and 100% interphase nuclei, respectively. FISH analysis on tissues collected after delivery revealed extraembryonic mosaicism. Conclusions. Extraembryonic tissue mosaicism is likely responsible for the false negative cfDNA screening result. This case illustrates that a negative result does not rule out the possibility of a fetus affected with a trisomy, as cffDNA is derived from the placenta and therefore may not accurately represent the fetal genetic information. PMID:26998368

  15. Clinical and molecular studies in full trisomy 22: Further delineation of the phenotype and review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Bacino, C.A.; Schreck, R.; Fischel-Ghodsian, N. [Cedars-Sinai Medical Center, Los Angeles, CA (United States)] [and others

    1995-05-08

    Trisomy 22 is commonly found among spontaneous abortions, second in frequency of occurrence only to trisomy 16. Most earlier reports of surviving trisomy 22 cases in the literature are thought to represent the product of unbalanced 11;22 translocations or the result of undetected mosaicism, since this condition is thought to manifest early embryonic or fetal lethality. We present two strikingly similar cases of non-mosaic trisomy 22 surviving to late gestation. In this paper we emphasize the unique phenotype of this trisomy which included intrauterine growth retardation, microcephaly, broad flat nasal bridge with epicanthal folds and ocular hypertelorism, microtia, variable cleft palate, webbed neck, congenital heart defects involving anomalous great vessels, anorectal and renal anomalies, and hypoplastic distal digits with thumb anomalies. We also explore why some cases survive to late gestation. Confined placental mosaicism, a frequent finding in other lethal trisomies, has been ruled out in one of the cases. Molecular studies done to assess the parental origin of the extra chromosome in the other case showed that the non-disjunction originated during maternal meiosis II. Parental origin of the extra chromosome does not seem to play a role in late survival for trisomy 22. 36 refs., 4 figs., 3 tabs.

  16. Could Digital PCR Be an Alternative as a Non-Invasive Prenatal Test for Trisomy 21: A Proof of Concept Study.

    Directory of Open Access Journals (Sweden)

    Laïla Allach El Khattabi

    Full Text Available NIPT for fetal aneuploidy by digital PCR has been hampered by the large number of PCR reactions needed to meet statistical requirements, preventing clinical application. Here, we designed an octoplex droplet digital PCR (ddPCR assay which allows increasing the number of available targets and thus overcomes statistical obstacles.After technical optimization of the multiplex PCR on mixtures of trisomic and euploid DNA, we performed a validation study on samples of plasma DNA from 213 pregnant women. Molecular counting of circulating cell-free DNA was performed using a mix of hydrolysis probes targeting chromosome 21 and a reference chromosome.The results of our validation experiments showed that ddPCR detected trisomy 21 even when the sample's trisomic DNA content is as low as 5%. In a validation study of plasma samples from 213 pregnant women, ddPCR discriminated clearly between the trisomy 21 and the euploidy groups.Our results demonstrate that digital PCR can meet the requirements for non-invasive prenatal testing of trisomy 21. This approach is technically simple, relatively cheap, easy to implement in a diagnostic setting and compatible with ethical concerns regarding access to nucleotide sequence information. These advantages make it a potential technique of choice for population-wide screening for trisomy 21 in pregnant women.

  17. Survival of trisomy 18 (Edwards syndrome) and trisomy 13 (Patau Syndrome) in England and Wales: 2004-2011.

    Science.gov (United States)

    Wu, Jianhua; Springett, Anna; Morris, Joan K

    2013-10-01

    The aim of this study is to determine the survival of live births with trisomy 18 and trisomy 13 and their variants. Information on live births with trisomy 18 or trisomy 13 recorded in the National Down Syndrome Cytogenetic Register (NDSCR) was linked by the NHS Information Centre to obtain information about survival. Survival was known for 326 (88%) of live births with trisomy 18 and 142 (82%) of live births with trisomy 13 born in England and Wales between 2004 and 2011. The median survival time for live births with full trisomy 18 was 14 days and with full trisomy 13 was 10 days, the 3-month survival was 20% and 18%, respectively, and the 1-year survival for both syndromes was 8%. The 1-year survival for live births with trisomy 18 mosaicism (n = 17) was 70%, for those with trisomy 13 mosaicism (n = 5) was 80% and for those with partial trisomy 13 (Robertsonian translocations) (n = 17) was 29%. This study is based on the largest data set on survival for live births with trisomy 18 and trisomy 13. Although median survival for these children is 2 weeks or less, about one in five survive for 3 months or more and about 1 in 12 survive for 1 year or more. We suggest that these survival rates are used in counselling as well as the median survival time. PMID:23949924

  18. Monozygotic twins with trisomy 18: a report of discordant phenotype.

    OpenAIRE

    Schlessel, J S; Brown, W T; Lysikiewicz, A.; Schiff, R.; Zaslav, A L

    1990-01-01

    The predicted incidence of liveborn monozygotic trisomy 18 twins is one per million births. The first case of liveborn monozygotic trisomy 18 twins was reported in 1989 and we report a second case in which striking phenotypic discordance existed. The probability of monozygotic trisomy 18 twinning and the mechanisms for phenotypic discordance in trisomic twins is discussed.

  19. Second pregnancy of trisomy 21 in a mother with mosaicism

    Institute of Scientific and Technical Information of China (English)

    CUI Ying-xia; HAO Li-jun; WANG Yun-hua; XIA Xin-yi; SHI Yi-chao; LU Hong-yong; YAO Bing; HUANG Yu-feng

    2007-01-01

    @@ In the case of a previous offspring with trisomy 21,recurrence risk for Down syndrome is about 1%.1 It may be due to chance, but the possibility of germline mosaicism for trisomy 21 in one of the parents has important implications for the recurrence. Here we report a young healthy mother, who has a second pregnancy of trisomy 21.

  20. Oral health needs in individuals with trisomy 18 and trisomy 13: Implications for dental professionals.

    Science.gov (United States)

    Bruns, Deborah; Martinez, Alyssa; Campbell, Emily All

    2016-01-01

    The purpose of this study was to examine oral health needs and dental care in individuals with trisomy 18 and trisomy 13 (full, mosaic, partial and other, mixed types). Primary feeding method was also examined. Data was collected from a parent-completed, mixed method survey (TRIS Survey). Mean age in months was 120.2 (range 38 to 394 months) and 133 (range 36 to 405 months), respectively, for trisomy 18 and trisomy 13 individuals. Results indicated the majority of individuals received routine dental care from their family dentist. Approximately 80% in both groups needed some form of specialized dental care. Close to 25% and 30% of trisomy 18 and trisomy 13 individuals, respectively, required hospital admission for specialized dental care. Responses indicated the presence of excessive plaque and tooth decay across the groups with a higher incidence for individuals with trisomy 13. Although not the primary form of intake, over half of the individuals received oral feedings. Implications for dental care and management are provided along with the need for additional research to confirm or disconfirm this study's findings. PMID:26585493

  1. Detecting aneuploidies of fetus by multiplex ligation-dependent probe amplification%多重连接探针扩增技术检测胎儿非整倍体异常

    Institute of Scientific and Technical Information of China (English)

    王凤羽; 马林先; 李聪敏; 张华; 丰慧根

    2012-01-01

    目的:探讨多重连接探针扩增技术(MLPA)在常见染色体非整倍体异常及其在产前诊断中的应用价值.方法:选择200份羊水标本,提取标本DNA,采用MLPA技术对样本染色体进行分析,并与传统染色体核型分析结果进行比较.结果:在200例样本中,除1例因羊水污染应用传统染色体核型分析失败外,其余检测结果与传统染色体核型分析方法的结果一致(21三体4例,18三体3例,13三体1例,X单体1例,X三体1例,其余190例正常).结论:MLPA技术分析胎儿染色体非整倍体异常是一种简单、快速且有效的方法.%Aim: To investigate the application value of the multiplex ligation-dependent probe amplification technique ( MLPA ) in common aneuploidies and prenatal diagnosis. Methods: A total of 200 amniotic fluid samples were collected. The DNA extracted from amniotic fluid was detected by MLPA. The results of chromosomal G-banding and MLPA of amniotic fluid were compared. Results:Out of 200 samples, the results of 199 by MLPA were consistent with traditional karyotype analysis, including4 trisomy 21,3 trisomy 18 ,1 trisomy 13 ,1 monosomy X,l female with extra X and 190 normal karyotype. Only one case with contamination was failed to reach conclusion by karyotype analysis. Conclusion: MLPA is a simple, rapid and efficacy method for analyzing aneuploids in amniotic fluid.

  2. Ultrasound features in trisomy 13 (Patau syndrome) and trisomy 18 (Edwards syndrome) in a consecutive series of 47 cases

    OpenAIRE

    Kroes, I.; Janssens, S; Defoort, P.

    2014-01-01

    Objective: To determine and list the variety of the predominant appeal signs leading to referral and their accompanying features found during specialized ultrasound evaluation in foetuses with trisomy 13 and trisomy 18. Materials and Methods: In a period of thirty years, 1110 cases of foetal malformations were detected during specialized echographic evaluation. 47 Of these cases were foetuses with trisomy 13 or trisomy 18. We evaluated the predominant signs leading to referral, the difference...

  3. Congenital Anomalies Associated with Trisomy 18 or Trisomy 13 : A Registry-Based Study in 16 European Countries, 2000-2011

    NARCIS (Netherlands)

    Springett, Anna; Wellesley, Diana; Greenlees, Ruth; Loane, Maria; Addor, Marie-Claude; Arriola, Larraitz; Bergman, Jorieke; Cavero-Carbonell, Clara; Csaky-Szunyogh, Melinda; Draper, Elizabeth S.; Garne, Ester; Gatt, Miriam; Haeusler, Martin; Khoshnood, Babak; Klungsoyr, Kari; Lynch, Catherine; Dias, Carlos Matias; McDonnell, Robert; Nelen, Vera; O'Mahony, Mary; Pierini, Anna; Queisser-Luft, Annette; Rankin, Judith; Rissmann, Anke; Rounding, Catherine; Stoianova, Sylvia; Tuckerz, David; Zymak-Zakutnia, Natalya; Morris, Joan K.

    2015-01-01

    The aim of this study was to examine the prevalence of trisomies 18 and 13 in Europe and the prevalence of associated anomalies. Twenty-five population-based registries in 16 European countries provided data from 2000-2011. Cases included live births, fetal deaths (20+ weeks' gestation), and termina

  4. Trisomy 18 mosaicism in a woman with normal intelligence, pigmentary dysplasia, and an 18 trisomic daughter

    Energy Technology Data Exchange (ETDEWEB)

    Ukita, Masahiko; Hasegawa, Masaaki; Nakahori, Takashi [Kurashiki Central Hospital (Japan)

    1997-01-20

    Survival beyond the age of 10 years is rare among 18-trisomic individuals. Most of these long-term survivors, when more than one tissue is studied, are normal/trisomy mosaics. They are usually mentally severely retarded with a variety of anomalies. There is another group of mosaic individuals: 7 women and a 13-year-old girl, with a low frequency of 18-trisomic cells, normal or mildly retarded intelligence, and minor anomalies. Two of them were diagnosed after delivering malformed stillborn infants. One of them was the mother of a trisomy 18 patient who was coincidentally found to have trisomy 18 mosaicism. Pigmentary dysplasia, previously called hypomelanosis of Ito, is a disorder with linear, swirly, or patchy, hypo- or hyperpigmented areas of skin, resulting from migration and interaction of melanoblasts of different pigmentary potential. The disorder is often accompanied by mosaic chromosomal abnormalities, including mosaic trisomy 18. Here we report a 26-year-old woman with low frequency trisomy 18 mosaicism, normal intelligence, and pigmentary dysplasia, who gave birth to an 18-trisomic girl. 12 refs., 1 fig.

  5. Prenatal Diagnosis of Bilateral Ectrodactyly and Radial Agenesis Associated with Trisomy 10 Mosaicism

    Directory of Open Access Journals (Sweden)

    Jonathan Lévy

    2013-01-01

    Full Text Available Ectrodactyly or split hand and foot malformations (SHFMs are rare malformations of the limbs, characterized by median clefts of the hands and feet, syndactyly, and aplasia and/or hypoplasia of the phalanges. They represent a clinically and genetically heterogeneous disorder, with both sporadic and familial cases. Most of the genomic rearrangements identified to date in some forms of SHFM are autosomal dominant traits, involving various chromosome regions. Bilateral radial ray defects comprise also a large heterogenous group of disorders, including trisomy 18, Fanconi anemia, and thrombocytopenia-absent-radius syndrome, not commonly associated with ectrodactyly. The present paper describes a case of ectrodactyly associated with bilateral radial ray defects, diagnosed in the first trimester of pregnancy, in a fetus affected by trisomy 10. Only four cases of sporadic and isolated ectrodactyly, diagnosed by ultrasonography between 14 and 22 weeks’ gestation, have been reported. To our knowledge, the present case is the first report of mosaic trisomy 10 associated with SHFM and radial aplasia. Trisomy 10 is a rare lethal chromosomal abnormality, most frequently found in abortion products. Only six liveborn mosaic trisomy 10 infants, with severe malformations, dead in early infancy, have been reported. A severe clinical syndrome can be defined, comprising ear abnormalities, cleft lip/palate, malformations of eyes, heart, and kidneys, and deformity of hands and feet and most often associated with death neonatally or in early infancy.

  6. Prenatal diagnosis of bilateral ectrodactyly and radial agenesis associated with trisomy 10 mosaicism.

    Science.gov (United States)

    Lévy, Jonathan; Jouannic, Jean-Marie; Saada, Julien; Dhombres, Ferdinand; Siffroi, Jean-Pierre; Portnoï, Marie-France

    2013-01-01

    Ectrodactyly or split hand and foot malformations (SHFMs) are rare malformations of the limbs, characterized by median clefts of the hands and feet, syndactyly, and aplasia and/or hypoplasia of the phalanges. They represent a clinically and genetically heterogeneous disorder, with both sporadic and familial cases. Most of the genomic rearrangements identified to date in some forms of SHFM are autosomal dominant traits, involving various chromosome regions. Bilateral radial ray defects comprise also a large heterogenous group of disorders, including trisomy 18, Fanconi anemia, and thrombocytopenia-absent-radius syndrome, not commonly associated with ectrodactyly. The present paper describes a case of ectrodactyly associated with bilateral radial ray defects, diagnosed in the first trimester of pregnancy, in a fetus affected by trisomy 10. Only four cases of sporadic and isolated ectrodactyly, diagnosed by ultrasonography between 14 and 22 weeks' gestation, have been reported. To our knowledge, the present case is the first report of mosaic trisomy 10 associated with SHFM and radial aplasia. Trisomy 10 is a rare lethal chromosomal abnormality, most frequently found in abortion products. Only six liveborn mosaic trisomy 10 infants, with severe malformations, dead in early infancy, have been reported. A severe clinical syndrome can be defined, comprising ear abnormalities, cleft lip/palate, malformations of eyes, heart, and kidneys, and deformity of hands and feet and most often associated with death neonatally or in early infancy. PMID:23401811

  7. Partial trisomy 8 (trisomy 8q2106 leads to 8qter).

    Science.gov (United States)

    Abuelo, D; Perl, D P; Henkle, C; Richardson, A

    1977-12-01

    A case of trisomy for part of the long arm of chromosome 8, confirmed by G-banding analysis, in a white male infant is described. The mother carried a reciprocal translocation between chromosome 8 and chromosome 13 (46,XX,t(8;13),(q21:q34). The patient had inherited the translocated chromosome 13 and was thus trisomic for the distal half of the long arm of chromosome 8. He had many of the clinical features of the full trisomy 8 syndrome. As compared with previously reported cases with trisomy of the distal end of chromosome 8, he was more dysmorphic and showed greater developmental retardation.

  8. Clinically abnormal case with paternally derived partial trisomy 8p23.3 to 8p12 including maternal isodisomy of 8p23.3: a case report

    Directory of Open Access Journals (Sweden)

    Thieme Heike

    2009-06-01

    Full Text Available Abstract Background Because of low copy repeats (LCRs and common inversion polymorphisms, the human chromosome 8p is prone to a number of recurrent rearrangements. Each of these rearrangements is associated with several phenotypic features. We report on a patient with various clinical malformations and developmental delay in connection with an inverted duplication event, involving chromosome 8p. Methods Chromosome analysis, multicolor banding analysis (MCB, extensive fluorescence in situ hybridization (FISH analysis and microsatellite analysis were performed. Results The karyotype was characterized in detail by multicolor banding (MCB, subtelomeric and centromere-near probes as 46,XY,dup(8(pter->p23.3::p12->p23.3::p23.3->qter. Additionally, microsatellite analysis revealed the paternal origin of the duplication and gave hints for a mitotic recombination involving about 6 MB in 8p23.3. Conclusion A comprehensive analysis of the derivative chromosome 8 suggested a previously unreported mechanism of formation, which included an early mitotic aberration leading to maternal isodisomy, followed by an inverted duplication of the 8p12p23.3 region.

  9. Possible risk factors for Down syndrome and sex chromosomal aneuploidy in Mysore, South India

    Directory of Open Access Journals (Sweden)

    Malini Suttur

    2007-01-01

    Full Text Available Background: Down syndrome (DS and sex chromosomal aneuploidy (SA are common chromosomal anomalies causing congenital malformations and mental retardation in humans. The well-established risk factor, advanced maternal age, was not found in many of the DS and SA cases in India, while the other possible risk factors have not been well studied. In view of this, the present study has been made. Materials and Methods: During the last 5 years, 150 clinically suspected DS and 25 SA cases were referred to our laboratory for chromosome investigation from major hospitals of Mysore city. Chromosome preparations were made from these patients after informed consent was obtained. Well-spread G-banded metaphase plates were analyzed by automated LEICA KARYO software. Two hundred and 100 randomly selected families belonging to different religions were used as controls for the DS and SA cases, respectively. Statistical analysis was carried out using logistic regression Results: Out of the 150 cases of DS, 122 had free trisomy 21, two were mosaic trisomy 21, and one had translocation. Logistic regression of case-control study of DS children revealed that the odds ratio of uncle-niece marriages, or second cousin marriages, or parents lived in rural region, or exposure of the parents to chemicals, or parents education status, or habits (tobacco/ alcohol used of father, or mother not undergone prenatal scanning, or mothers with previous abortions were significant when all the variables of that category were used one at a time. Exposure of the parents to chemicals, parents′ educational status, habits (tobacco/alcohol use of the father, mother not undergone prenatal scanning, and history of previous abortions were significant when all the variables of that category were used one at a time. Similarly, except for consanguinity, history of previous abortions, and mother not undergone prenatal scanning, all other factors showed significant odds ratios in SA cases

  10. Could sperm aneuploidy rate determination be used as a predictive test before intracytoplasmic sperm injection?

    Science.gov (United States)

    Petit, François M; Frydman, Nelly; Benkhalifa, Moncef; Le Du, Anne; Aboura, Azzedine; Fanchin, Renato; Frydman, Rene; Tachdjian, Gerard

    2005-01-01

    Chromosome abnormalities in embryos are a major cause of implantation and development failures. Some couples with normal karyotypes have repeated implantation failures after intracytoplasmic sperm injection (ICSI). In order to value patients at risk for genetic ICSI failures and the validity of sperm aneuploidy analysis, we have studied cytogenetic abnormalities in sperm from ICSI patients. Twenty-nine patients with normal karyotypes were included. Ten patients had at least 4 ICSI treatments without pregnancy (group A). Nine patients had a pregnancy after 1 to 3 ICSI treatments (group B). Ten fertile men with normal semen parameters were studied as controls (group C). Fluorescent in situ hybridization (FISH) was used for sperm nucleus cytogenetic analysis using chromosomes 8, 9, 13, 18, 21, X, and Y specific probes. Aneuploidy for each chromosome and diploidy rates were significantly higher in group A than in group B and in group B than in group C (P < .05). Considering each patient in groups A and B, aneuploidy rate for each chromosome was too variable to be considered as a significant test. We proposed analysis of the total sperm aneuploidy. Chromosomal sperm nuclei profile could be used as a predictive biological test before ICSI in order to improve genetic counseling for oligoasthenoteratozoospermia patients.

  11. An Optimized Method for Accurate Fetal Sex Prediction and Sex Chromosome Aneuploidy Detection in Non-Invasive Prenatal Testing.

    Science.gov (United States)

    Wang, Ting; He, Quanze; Li, Haibo; Ding, Jie; Wen, Ping; Zhang, Qin; Xiang, Jingjing; Li, Qiong; Xuan, Liming; Kong, Lingyin; Mao, Yan; Zhu, Yijun; Shen, Jingjing; Liang, Bo; Li, Hong

    2016-01-01

    Massively parallel sequencing (MPS) combined with bioinformatic analysis has been widely applied to detect fetal chromosomal aneuploidies such as trisomy 21, 18, 13 and sex chromosome aneuploidies (SCAs) by sequencing cell-free fetal DNA (cffDNA) from maternal plasma, so-called non-invasive prenatal testing (NIPT). However, many technical challenges, such as dependency on correct fetal sex prediction, large variations of chromosome Y measurement and high sensitivity to random reads mapping, may result in higher false negative rate (FNR) and false positive rate (FPR) in fetal sex prediction as well as in SCAs detection. Here, we developed an optimized method to improve the accuracy of the current method by filtering out randomly mapped reads in six specific regions of the Y chromosome. The method reduces the FNR and FPR of fetal sex prediction from nearly 1% to 0.01% and 0.06%, respectively and works robustly under conditions of low fetal DNA concentration (1%) in testing and simulation of 92 samples. The optimized method was further confirmed by large scale testing (1590 samples), suggesting that it is reliable and robust enough for clinical testing.

  12. An Optimized Method for Accurate Fetal Sex Prediction and Sex Chromosome Aneuploidy Detection in Non-Invasive Prenatal Testing.

    Directory of Open Access Journals (Sweden)

    Ting Wang

    Full Text Available Massively parallel sequencing (MPS combined with bioinformatic analysis has been widely applied to detect fetal chromosomal aneuploidies such as trisomy 21, 18, 13 and sex chromosome aneuploidies (SCAs by sequencing cell-free fetal DNA (cffDNA from maternal plasma, so-called non-invasive prenatal testing (NIPT. However, many technical challenges, such as dependency on correct fetal sex prediction, large variations of chromosome Y measurement and high sensitivity to random reads mapping, may result in higher false negative rate (FNR and false positive rate (FPR in fetal sex prediction as well as in SCAs detection. Here, we developed an optimized method to improve the accuracy of the current method by filtering out randomly mapped reads in six specific regions of the Y chromosome. The method reduces the FNR and FPR of fetal sex prediction from nearly 1% to 0.01% and 0.06%, respectively and works robustly under conditions of low fetal DNA concentration (1% in testing and simulation of 92 samples. The optimized method was further confirmed by large scale testing (1590 samples, suggesting that it is reliable and robust enough for clinical testing.

  13. An Optimized Method for Accurate Fetal Sex Prediction and Sex Chromosome Aneuploidy Detection in Non-Invasive Prenatal Testing

    Science.gov (United States)

    Li, Haibo; Ding, Jie; Wen, Ping; Zhang, Qin; Xiang, Jingjing; Li, Qiong; Xuan, Liming; Kong, Lingyin; Mao, Yan; Zhu, Yijun; Shen, Jingjing; Liang, Bo; Li, Hong

    2016-01-01

    Massively parallel sequencing (MPS) combined with bioinformatic analysis has been widely applied to detect fetal chromosomal aneuploidies such as trisomy 21, 18, 13 and sex chromosome aneuploidies (SCAs) by sequencing cell-free fetal DNA (cffDNA) from maternal plasma, so-called non-invasive prenatal testing (NIPT). However, many technical challenges, such as dependency on correct fetal sex prediction, large variations of chromosome Y measurement and high sensitivity to random reads mapping, may result in higher false negative rate (FNR) and false positive rate (FPR) in fetal sex prediction as well as in SCAs detection. Here, we developed an optimized method to improve the accuracy of the current method by filtering out randomly mapped reads in six specific regions of the Y chromosome. The method reduces the FNR and FPR of fetal sex prediction from nearly 1% to 0.01% and 0.06%, respectively and works robustly under conditions of low fetal DNA concentration (1%) in testing and simulation of 92 samples. The optimized method was further confirmed by large scale testing (1590 samples), suggesting that it is reliable and robust enough for clinical testing. PMID:27441628

  14. Cardiac function in trisomy 21 fetuses

    NARCIS (Netherlands)

    S.A.B. Clur; K. Oude Rengerink; J. Ottenkamp; C.M. Bilardo

    2011-01-01

    Objectives Trisomy 21 is associated with an increased nuchal translucency thickness (NT), abnormal ductus venosus (DV) flow at 11-14 weeks' gestation and congenital heart defects (CHD), and cardiac dysfunction has been hypothesized as the link between them. We therefore aimed to investigate whether

  15. Dermatoglyphic Patterns in 9p Trisomy Syndrome

    Science.gov (United States)

    Loesch, Danuta; Czyzewska, Jadwiga

    1978-01-01

    Thirty-seven palm prints and 30 sole prints of people with 9p trisomy (a chromosomal anomaly associated with abnormal limb development) were analysed with respect to frequency distribution of loops and triradii on palms, soles, and fingertips, as well as of the total pattern types. (Author)

  16. Sacrococcygeal Teratoma associated with Trisomy 13.

    Science.gov (United States)

    Dorum, Bayram Ali; Köksal, Nilgün; Özkan, Hilal; Karakaya, Sabahattin; Akgül, Ahsen Karagözlü

    2016-01-01

    Sacrococcygeal teratoma (SCT) is rarely associated with syndromes. We report a female newborn with a prenatal diagnosis of small sacrococcygeal teratoma and postnatally diagnosed as having trisomy 13. The sacrococcygeal teratoma was excised. It was reported as mature teratoma. The child succumbed to sepsis postoperatively. PMID:27398323

  17. MicroRNA-15a and -16-1 act via MYB to elevate fetal hemoglobin expression in human trisomy 13.

    Science.gov (United States)

    Sankaran, Vijay G; Menne, Tobias F; Šćepanović, Danilo; Vergilio, Jo-Anne; Ji, Peng; Kim, Jinkuk; Thiru, Prathapan; Orkin, Stuart H; Lander, Eric S; Lodish, Harvey F

    2011-01-25

    Many human aneuploidy syndromes have unique phenotypic consequences, but in most instances it is unclear whether these phenotypes are attributable to alterations in the dosage of specific genes. In human trisomy 13, there is delayed switching and persistence of fetal hemoglobin (HbF) and elevation of embryonic hemoglobin in newborns. Using partial trisomy cases, we mapped this trait to chromosomal band 13q14; by examining the genes in this region, two microRNAs, miR-15a and -16-1, appear as top candidates for the elevated HbF levels. Indeed, increased expression of these microRNAs in primary human erythroid progenitor cells results in elevated fetal and embryonic hemoglobin gene expression. Moreover, we show that a direct target of these microRNAs, MYB, plays an important role in silencing the fetal and embryonic hemoglobin genes. Thus we demonstrate how the developmental regulation of a clinically important human trait can be better understood through the genetic and functional study of aneuploidy syndromes and suggest that miR-15a, -16-1, and MYB may be important therapeutic targets to increase HbF levels in patients with sickle cell disease and β-thalassemia.

  18. Clinical features and survival in individuals with trisomy 18: A retrospective one-center study of 44 patients who received intensive care treatments.

    Science.gov (United States)

    Imataka, George; Suzumura, Hiroshi; Arisaka, Osamu

    2016-03-01

    Trisomy 18 syndrome is a common autosomal aneuploidy chromosomal abnormality caused by the presence of extra chromosome 18 that leads to malformations of various parts of the body. In this study, we retrospectively investigated the effect of the medical progression and prognosis of 44 cases of trisomy 18, admitted to our neonatal intensive care unit between 1992 and 2013. The patients were divided into group A (n=20, 1992‑2002) and group B (n=24, 2003‑2012). Following delivery, karyotype, gender, gestational weeks, birth place, cesarean section, Apgar score and birth weight were analyzed using the Fisher's exact test, unpaired t‑test and Mann‑Whitney U test. Based on the statistical results, a comparison was made of the two groups and no significant differences were observed. Clinical data of major complications, mechanical ventilation, discharge from hospital and survival days were reviewed for the cases of trisomy 18. Of the 44 patients, 42 had cardiac anomaly, 16 had esophageal atresia, and 3 patients had brain anomaly. Ventilation treatment was performed in 29 cases (65.9%) and an increased percentage was identified in group B patients. The percentage survival was estimated using Kaplan‑Meier curves and the two groups were analyzed using the generalized Wilcoxon test. Improvement in life prognosis was observed in group B as compared to group A. The log‑rank test was used to assess survey periods of 180 days, 1 year, and the entire observation period. Although significant differences were observed for the prognosis of trisomy 18 at 180 days after birth, after 1 year and the entire survey period after birth, the significant differences were not confirmed. In conclusion, results of the present study provide information concerning genetic counseling for parents/guardians and life prognosis, prior to applying intensive management to newborns with trisomy 18. PMID:26820816

  19. Laboratory Exercises to Examine Recombination & Aneuploidy in "Drosophila"

    Science.gov (United States)

    Venema, Dennis R.

    2009-01-01

    Chromosomal aneuploidy, a deviation from an exact multiple of an organism's haploid chromosome number, is a difficult concept for students to master. Aneuploidy arising from chromosomal non-disjunction (NDJ) is particularly problematic for students, since it arises in the context of meiosis, itself a challenging subject. Students learning NDJ are…

  20. Prospective studies on children with sex chromosome aneuploidy

    Energy Technology Data Exchange (ETDEWEB)

    Ratcliffe, S.G.; Paul, N.

    1986-01-01

    This book contains 11 selections. Some of the titles are: Growth and Development from Early to Midadolescence of Children with X and Y Chromosome Aneuploidy: The Toronto Study; Sex Chromomal Aneuploidy: Perspective and Longitudinal Studies; Psychologic Study of XYY and XXY Men; and Cellular and Molecular Studies in Human Chromosomal Diseases.

  1. Mapping the stability of human brain asymmetry across five sex-chromosome aneuploidies.

    Science.gov (United States)

    Lin, Amy; Clasen, Liv; Lee, Nancy Raitano; Wallace, Gregory L; Lalonde, Francois; Blumenthal, Jonathan; Giedd, Jay N; Raznahan, Armin

    2015-01-01

    The human brain displays stereotyped and early emerging patterns of cortical asymmetry in health. It is unclear if these asymmetries are highly sensitive to genetic and environmental variation or fundamental features of the brain that can survive severe developmental perturbations. To address this question, we mapped cortical thickness (CT) asymmetry in a group of genetically defined disorders known to impact CT development. Participants included 137 youth with one of five sex-chromosome aneuploidies [SCAs; XXX (n = 28), XXY (n = 58), XYY (n = 26), XXYY (n = 20), and XXXXY (n = 5)], and 169 age-matched typically developing controls (80 female). In controls, we replicated previously reported rightward inferior frontal and leftward lateral parietal CT asymmetry. These opposing frontoparietal CT asymmetries were broadly preserved in all five SCA groups. However, we also detected foci of shifting CT asymmetry with aneuploidy, which fell almost exclusively within regions of significant CT asymmetry in controls. Specifically, X-chromosome aneuploidy accentuated normative rightward inferior frontal asymmetries, while Y-chromosome aneuploidy reversed normative rightward medial prefrontal and lateral temporal asymmetries. These findings indicate that (1) the stereotyped normative pattern of opposing frontoparietal CT asymmetry arises from developmental mechanisms that can withstand gross chromosomal aneuploidy and (2) X and Y chromosomes can exert focal, nonoverlapping and directionally opposed influences on CT asymmetry within cortical regions of significant asymmetry in health. Our study attests to the resilience of developmental mechanisms that support the global patterning of CT asymmetry in humans, and motivates future research into the molecular bases and functional consequences of sex chromosome dosage effects on CT asymmetry.

  2. Trisomy greatly enhances interstitial crossing over in a translocation heterozygote of Secale

    NARCIS (Netherlands)

    Sybenga, J.; Verhaar, H.M.; Botje, D.G.A.

    2012-01-01

    Chromosomal rearrangements, including reciprocal translocations, may prevent recombinational transfer of genes from a donor genotype to a recipient, especially when the gene is located in an interstitial segment. The effect of trisomy of chromosome arm 1RS on recombination was studied in translocati

  3. 多重定量荧光PCR在胎儿常见染色体非整倍体快速诊断中的应用%Application of multiple quantitative fluorescence polymerase chain reaction approach for rapid prenatal diagnosis of common chromosome aneuploidies

    Institute of Scientific and Technical Information of China (English)

    胡婷; 刘洪倩; 朱红梅; 王婧; 张海霞; 祝茜; 赖怡; 秦利; 王和

    2014-01-01

    目的 探讨多重定量荧光PCR(quantitative fluorescence polymerase chain reaction,QFPCR)技术在胎儿常见染色体非整倍体异常快速诊断中的应用.方法 用QF-PCR技术对我院4649名行羊膜腔穿刺术孕妇的4760份羊水样本21、18、13、X和Y染色体数目进行分析,并与染色体核型分析结果进行比较.结果 QF-PCR检测成功率为98.4%.QF-PCR检测出21、18、13、X及Y染色体非整倍体48例(2例核型为46,XY,rob(13∶21),+21;4例为双胎之一21三体),均与核型分析结果一致,5种常见染色体非整倍体异常分析敏感性和特异性均为100%;检出1例21三体嵌合体及4例性染色体异常的嵌合体(1例核型分析漏诊);QF-PCR漏诊4例性染色体嵌合体;染色体核型分析失败的64例样本,QF-PCR检测均得到结果.QF-PCR检测结果与核型分析符合率为98.3%.结论 QF-PCR技术可快速、准确的诊断21、18、13、X及Y染色体非整倍体,并能检出部分嵌合体,作为染色体核型分析的有效补充,在快速产前诊断中具有重要临床实用价值.%Objective To assess the value of multiple quantitative fluorescence polymerase chain reaction (QF-PCR) approach for rapid prenatal diagnosis of common chromosomal aneuploidies.Methods A total of 4760 amniotic samples from 4649 pregnant women were analyzed with QF-PCR for 21,18,13,X and Y aneuploidies,and the results were compared with those of karyotype analysis.Results The overall success rate for QF-PCR was 98.4%.All the 48 cases of 21,18,13,X and Y aneuploidies (including 2 case of 46,XY,rob(13 ∶ 21),+ 21; 4 trisomy 21 in 4 twins) were detected by QF-PCR,with the overall sensibility and specificity both reaching 100%.One mosaicism of trisomy 21 and 4 mosaicisms of sex chromosome (1 misdiagnosed by karyotype analysis) were also detected by QF-PCR.Four mosaicisms of sex chromosome were verified as missed diagnosis.All the 64 cases failed by karyotype analysis were successfully analyzed by the

  4. Recurrence risks for trisomies 13, 18, and 21.

    Science.gov (United States)

    De Souza, Elizabeth; Halliday, Jane; Chan, Annabelle; Bower, Carol; Morris, Joan K

    2009-12-01

    The objective was to establish whether the risk of trisomies 13, 18, and 21 (Patau, Edwards, and Down syndrome, respectively) in a subsequent pregnancy is raised for women who have had a previous pregnancy with trisomy 13, 18, or 21. Birth defect register data were used to investigate this issue. Pregnancy data from three Australian population-based birth defect registers contained 5,906 women with a previous trisomy 13, 18, or 21 pregnancy in whom there were 3,713 subsequent pregnancies, 75 of which were trisomic. Relative risk of subsequent trisomy at 15 weeks gestation was estimated by comparing the observed number of subsequent trisomies with the expected number of subsequent trisomies based on maternal age-related risk. There was evidence of increased risk of the same trisomy subsequent to a previous pregnancy with trisomy 13 or 18 (RR = 3.8 (1.5, 7.9)), the increase in risk being greater for women aged under 35 at the previous trisomic pregnancy (RR = 7.8 (2.1, 20.2)). There was also evidence of increased risk of trisomy 21 subsequent to previous trisomy 21 (RR = 2.2 (1.6, 2.9)), again higher in women under 35 at previous affected pregnancy (RR = 3.5 (2.1, 5.5)). There was a suggestion that the risk of a different trisomy subsequent to trisomy 21 may also be increased (RR = 1.4 (0.7, 2.5)). In conclusion, women who have had a previous trisomic pregnancy, particularly those under 35 years of age at the time, appear to be at an increased risk of future pregnancies being trisomic. PMID:19921649

  5. Fetal Aneuploidy Detection by Cell-Free DNA Sequencing for Multiple Pregnancies and Quality Issues with Vanishing Twins

    Directory of Open Access Journals (Sweden)

    Sebastian Grömminger

    2014-06-01

    Full Text Available Non-invasive prenatal testing (NIPT by random massively parallel sequencing of maternal plasma DNA for multiple pregnancies is a promising new option for prenatal care since conventional non-invasive screening for fetal trisomies 21, 18 and 13 has limitations and invasive diagnostic methods bear a higher risk for procedure related fetal losses in the case of multiple gestations compared to singletons. In this study, in a retrospective blinded analysis of stored twin samples, all 16 samples have been determined correctly, with four trisomy 21 positive and 12 trisomy negative samples. In the prospective part of the study, 40 blood samples from women with multiple pregnancies have been analyzed (two triplets and 38 twins, with two correctly identified trisomy 21 cases, confirmed by karyotyping. The remaining 38 samples, including the two triplet pregnancies, had trisomy negative results. However, NIPT is also prone to quality issues in case of multiple gestations: the minimum total amount of cell-free fetal DNA must be higher to reach a comparable sensitivity and vanishing twins may cause results that do not represent the genetics of the living sibling, as described in two case reports.

  6. Increased frequency of aneuploidy in long-lived spermatozoa.

    Science.gov (United States)

    You, Young-Ah; Park, Yoo-Jin; Kwon, Woo-Sung; Yoon, Sung-Jae; Ryu, Buom-Yong; Kim, Young Ju; Pang, Myung-Geol

    2014-01-01

    Aneuploidy commonly causes spontaneous abortions, stillbirths, and aneuploid births in humans. Notably, the majority of sex chromosome aneuploidies in live births have a paternal origin. An increased frequency of aneuploidy is also associated with male infertility. However, the dynamics and behavior of aneuploid spermatozoa during fertilization in humans have not been studied in detail. Therefore, we compared the frequency of aneuploidy and euploidy in live spermatozoa from normozoospermic men over a 3-day period. To assess the dynamics and behavior of aneuploid spermatozoa, we simultaneously evaluated sperm viability using the hypo-osmotic swelling test and sperm aneuploidy using fluorescence in situ hybridization. Whereas the frequency of viable euploid spermatozoa significantly decreased over 3 days, the frequency of viable spermatozoa with aneuploidy interestingly showed a time-dependent increase. In addition, spermatozoa with abnormal sex chromosomes survived longer. To compared with spermatozoa with other swelling patterns, those with tail-tip swelling patterns had a lower frequency of aneuploidy at all time points. This study revealed the novel finding that the frequency of aneuploid spermatozoa with fertilization capability significantly increased compared to that of euploid spermatozoa over 3 days, suggesting that aneuploid spermatozoa can survive longer than euploid spermatozoa and have a greater chance of fertilizing oocytes.

  7. Increased frequency of aneuploidy in long-lived spermatozoa.

    Directory of Open Access Journals (Sweden)

    Young-Ah You

    Full Text Available Aneuploidy commonly causes spontaneous abortions, stillbirths, and aneuploid births in humans. Notably, the majority of sex chromosome aneuploidies in live births have a paternal origin. An increased frequency of aneuploidy is also associated with male infertility. However, the dynamics and behavior of aneuploid spermatozoa during fertilization in humans have not been studied in detail. Therefore, we compared the frequency of aneuploidy and euploidy in live spermatozoa from normozoospermic men over a 3-day period. To assess the dynamics and behavior of aneuploid spermatozoa, we simultaneously evaluated sperm viability using the hypo-osmotic swelling test and sperm aneuploidy using fluorescence in situ hybridization. Whereas the frequency of viable euploid spermatozoa significantly decreased over 3 days, the frequency of viable spermatozoa with aneuploidy interestingly showed a time-dependent increase. In addition, spermatozoa with abnormal sex chromosomes survived longer. To compared with spermatozoa with other swelling patterns, those with tail-tip swelling patterns had a lower frequency of aneuploidy at all time points. This study revealed the novel finding that the frequency of aneuploid spermatozoa with fertilization capability significantly increased compared to that of euploid spermatozoa over 3 days, suggesting that aneuploid spermatozoa can survive longer than euploid spermatozoa and have a greater chance of fertilizing oocytes.

  8. Mechanisms and chemical induction of aneuploidy in rodent germ cells

    Energy Technology Data Exchange (ETDEWEB)

    Mailhes, J B; Marchetti, F

    2004-10-15

    The objective of this review is to suggest that the advances being made in our understanding of the molecular events surrounding chromosome segregation in non-mammalian and somatic cell models be considered when designing experiments for studying aneuploidy in mammalian germ cells. Accurate chromosome segregation requires the temporal control and unique interactions among a vast array of proteins and cellular organelles. Abnormal function and temporal disarray among these, and others to be inidentified, biochemical reactions and cellular organelles have the potential for predisposing cells to aneuploidy. Although numerous studies have demonstrated that certain chemicals (mainly those that alter microtubule function) can induce aneuploidy in mammalian germ cells, it seems relevant to point out that such data can be influenced by gender, meiotic stage, and time of cell-fixation post-treatment. Additionally, a consensus has not been reached regarding which of several germ cell aneuploidy assays most accurately reflects the human condition. More recent studies have shown that certain kinase, phosphatase, proteasome, and topoisomerase inhibitors can also induce aneuploidy in rodent germ cells. We suggest that molecular approaches be prudently incorporated into mammalian germ cell aneuploidy research in order to eventually understand the causes and mechanisms of human aneuploidy. Such an enormous undertaking would benefit from collaboration among scientists representing several disciplines.

  9. Molecular origin of mitotic aneuploidies in preimplantation embryos.

    Science.gov (United States)

    Mantikou, Eleni; Wong, Kai Mee; Repping, Sjoerd; Mastenbroek, Sebastiaan

    2012-12-01

    Mitotic errors are common in human preimplantation embryos. The occurrence of mitotic errors is highest during the first three cleavages after fertilization and as a result about three quarters of human preimplantation embryos show aneuploidies and are chromosomally mosaic at day three of development. The origin of these preimplantation mitotic aneuploidies and the molecular mechanisms involved are being discussed in this review. At later developmental stages the mitotic aneuploidy rate is lower. Mechanisms such as cell arrest, apoptosis, active correction of the aneuploidies and preferential allocation of the aneuploid cells to the extra-embryonic tissues could underlie this lower rate. Understanding the mechanisms that cause mitotic aneuploidies in human preimplantation embryos and the way human preimplantation embryos deal with these aneuploidies might lead to ways to limit the occurrence of aneuploidies, in order to ultimately increase the quality of embryos and with that the likelihood of a successful pregnancy in IVF/ICSI. This article is part of a Special Issue entitled: Molecular Genetics of Human Reproductive Failure. PMID:22771499

  10. Alobar holoprosencephaly and Trisomy 13 (Patau syndrome

    Directory of Open Access Journals (Sweden)

    Andressa Dias Costa

    2013-06-01

    Full Text Available Holoprosencephaly (HPE is a congenital defect of the brain, median structures, and face resulting from an incomplete cleavage of the primitive brain during early embryogenesis. The authors report a case of trisomy 13 syndrome diagnosed at prenatal follow up. The preterm newborn lived only 5 hours, and died because of severe respiratory failure. The autopsy findings disclosed facial, skull, limbs, cardiac, and cerebral malformations. Among the latter, the presence of alobar HPE, the central theme of this report, was evident. The most common nonrandom chromosomal abnormality in patients with HPE is trisomy 13. The most severe variant, namely alobar HPE, is shown in this case report. Discussion on this severe anomaly, along with the case report with details of Patau’s syndrome, is the goal of this report.

  11. Alobar holoprosencephaly and Trisomy 13 (Patau syndrome)

    OpenAIRE

    Andressa Dias Costa; Regina Schultz; Sérgio Rosemberg

    2013-01-01

    Holoprosencephaly (HPE) is a congenital defect of the brain, median structures, and face resulting from an incomplete cleavage of the primitive brain during early embryogenesis. The authors report a case of trisomy 13 syndrome diagnosed at prenatal follow up. The preterm newborn lived only 5 hours, and died because of severe respiratory failure. The autopsy findings disclosed facial, skull, limbs, cardiac, and cerebral malformations. Among the latter, the presence of alobar HPE, the central t...

  12. Mosaic partial trisomy 17q2

    OpenAIRE

    King, P. A.; Ghosh, A; Tang, M

    1991-01-01

    Examination of an infant born after prenatal diagnosis of mosaic partial trisomy 17q2 showed the unique phenotypic features of this chromosomal abnormality, that is, frontal bossing, large mouth, brachyrhizomelia, and hexadactyly. Amniocentesis was performed because of polyhydramnios and ultrasound diagnosis of fetal craniofacial dysmorphology and rhizomelic shortening of the limbs. Chromosomal mosaicism was restricted to fetal tissue and amniotic fluid cells. The placental chromosomal comple...

  13. Lymphocyte respiration in children with Trisomy 21

    Directory of Open Access Journals (Sweden)

    Aburawi Elhadi H

    2012-12-01

    Full Text Available Abstract Background This study measured lymphocyte mitochondrial O2 consumption (cellular respiration in children with trisomy 21. Methods Peripheral blood mononuclear cells were isolated from whole blood of trisomy 21 and control children and these cells were immediately used to measure cellular respiration rate. [O2] was determined as a function of time from the phosphorescence decay rates (1/τ of Pd (II-meso-tetra-(4-sulfonatophenyl-tetrabenzoporphyrin. In sealed vials containing lymphocytes and glucose as a respiratory substrate, [O2] declined linearly with time, confirming the zero-order kinetics of O2 conversion to H2O by cytochrome oxidase. The rate of respiration (k, in μM O2 min-1, thus, was the negative of the slope of [O2] vs. time. Cyanide inhibited O2 consumption, confirming that oxidation occurred in the mitochondrial respiratory chain. Results For control children (age = 8.8 ± 5.6 years, n = 26, the mean (± SD value of kc (in μM O2 per min per 107 cells was 1.36 ± 0.79 (coefficient of variation, Cv = 58%; median = 1.17; range = 0.60 to 3.12; -2SD = 0.61. For children with trisomy 21 (age = 7.2 ± 4.6 years, n = 26, the values of kc were 0.82 ± 0.62 (Cv = 76%; median = 0.60; range = 0.20 to 2.80, pp6.1 mU/L. Fourteen of 26 (54% children with trisomy 21 had kc values of 0.20 to 0.60 (i.e., kc positively correlated with body-mass index (BMI, R >0.302, serum creatinine (R >0.507, blood urea nitrogen (BUN, R >0.535 and albumin (R >0.446. Conclusions Children with trisomy 21 in this study have reduced lymphocyte bioenergetics. The clinical importance of this finding requires further studies.

  14. Microchimeric Cells, Sex Chromosome Aneuploidies and Cancer.

    Science.gov (United States)

    Korkmaz, Deniz Taştemir; Demirhan, Osman; Abat, Deniz; Demirberk, Bülent; Tunç, Erdal; Kuleci, Sedat

    2015-09-01

    The phenomenon of feta-maternal microchimerisms inspires numerous questions. Many questions remain to be answered regarding this new avenue of genetics. The X and Y chromosomes have been associated with malignancy in different types of human tumors. We aimed to investigate the numerical aberrations of chromosomes X and Y in lung cancer (LC) and bladder cancer (BC) and review recent evidence for possible roles of microchimeric cells (McCs) in these cancers. We carried out cytogenetic analysis of the tumor and blood sampling in 52 cases of people with BC and LC, and also with 30 healthy people. A total of 48 (92.3 %) of the patients revealed sex chromosome aneuploidies (SCAs). A total SCAs was found in 9.8 % of 2282 cells that were analyzed as one or more cells in each case. The 68 and 95 SCAs were found in the 1952 (8.4 %) cells in peripheral blood, and 41 and 19 SCAs in the 330 (18.2 %) cells in the tumoral tissues respectively. There was a significant difference in the frequencies of SCAs between the patients and the control groups determined by the Fischer's Exact Test (p chromosome monosomies. Largely a Y chromosome loss was present in 77.8 % of the men, and the 47, XXY karyotype was found in 33.3 % of them. The second most common SCA was monosomy X, and was found in 71.4 % of the women. McCs were observed in 26.9 % of the 52 patients, and the frequencies of McCs were higher in the blood than in the tissues (p aneuploidies of X and Y chromosomes play a role in the pathogenesis of cancers.

  15. Rothmund-Thomson syndrome associated with trisomy 8 mosaicism.

    OpenAIRE

    Ying, K L; J. Oizumi; Curry, C J

    1990-01-01

    This report describes a boy with Rothmund-Thomson syndrome associated with trisomy 8 mosaicism. The patient presented with typical features of Rothmund-Thomson syndrome but some of the features often seen in trisomy 8 mosaics were also observed in him. The possibility that the two disorders might share a common pathogenesis is postulated.

  16. Successful Noninvasive Trisomy 18 Detection Using Single Molecule Sequencing

    NARCIS (Netherlands)

    van den Oever, Jessica M. E.; Balkassmi, Sahila; Johansson, Lennart F.; van Scheltema, Phebe N. Adama; Suijkerbuijk, Ron F.; Hoffer, Mariette J. V.; Sinke, Richard J.; Bakker, Egbert; Sikkema-Raddatz, Birgit; Boon, Elles M. J.

    2013-01-01

    BACKGROUND: Noninvasive trisomy 21 detection performed by use of massively parallel sequencing is achievable with high diagnostic sensitivity and low false-positive rates. Detection of fetal trisomy 18 and 13 has been reported as well but seems to be less accurate with the use of this approach. The

  17. Social Deficits in Male Children and Adolescents with Sex Chromosome Aneuploidy: A Comparison of XXY, XYY, and XXYY Syndromes

    Science.gov (United States)

    Cordeiro, Lisa; Tartaglia, Nicole; Roeltgen, David; Ross, Judith

    2012-01-01

    We compare social skills in three groups of males with sex chromosome aneuploidies (SCAs) using the Social Responsiveness Scale (SRS). Participants included males with XXY (N = 102, M = 10.08 years), XYY (N = 40, M = 9.93 years), and XXYY (N = 32, M = 11.57 years). XXY had lower (better) SRS scores compared to XYY and XXYY. Scores were not…

  18. Phenotype-genotype discordance in congenital malformations with communication disorders resembling trisomy 18 (Edwards syndrome)

    OpenAIRE

    Pruszewicz, Antoni; Wiskirska-Woźnica, Bożena; Wojnowski, Waldemar; Czerniejewska, Hanna; Jackowska, Joanna; Jarmuż, Małgorzata; Szyfter, Krzysztof; Leszczyńska, Małgorzata

    2014-01-01

    Patient: Female, 6 Final Diagnosis: Phenotype-genotype discordance in congenital malformations with communication disorders resembling trisomy 18 (Edwards syndrome) Symptoms: — Medication: — Clinical Procedure: — Specialty: Otolaryngology Objective: Congenital defects Background: Communication process disorders are very frequent in rare cases of chromosomal aberrations (deletions, insertions, and trisomies) such as Down syndrome (trisomy 21), Turner syndrome, Edwards syndrome (trisomy 18), or...

  19. Trisomy 2p: Analysis of unusual phenotypic findings

    Energy Technology Data Exchange (ETDEWEB)

    Lurie, I.W.; Ilyina, H.G.; Gurevich, D.B. [Belorussian Research Institute of Hereditary Disease, Minsk (Russian Federation)] [and others

    1995-01-16

    We present three probands with partial trisomies 2p21-23 due to ins(4;2)(q21;p21p23) pat, 2p23-pter due to t(2;4)(p23;q35)mat, and 2p21-pter due to t(2;11)(p21;q23.3)mat. More than 50 cases of partial trisomy 2p have been reviewed and some abnormalities, unusual for most other types of structural autosomal imbalance, have been found in patients with inherited forms of 2p trisomy and in their non-karyotyped sibs. Neural tube defects (anencephaly, occipital encephalocele, and spina bifida) were found in five probands and 4/6 affected non-karyotyped sibs. The only triplicated segment common to all was 2p24. Different forms of {open_quotes}broncho-pulmonary a/hypoplasia{close_quotes} (including two cases of lung agenesis) were described in four patients (overlapping triplicated segment was 2p21-p25). Three patients (with overlapping triplicated segment 2p23-p25) had diaphragmatic hernia. Abnormal rotation of the heart or L-transposition of large vessels (with or without visceral heterotaxia) was found in two infants (overlapping triplicated segment 2p23-p24). In two patients with common triplicated segment 2p22.3-p25, neuroblastoma has been described. The occurrence of all these defects may be explained either by the action of the same gene(s) mapped to 2p24 or by action of some independent factors located in different segments of the short arm. Although the latter hypothesis is much less probable, it can not be rejected at the present time. We propose the existence of a genetic system controlling surveillance of an abnormal embryo to explain the phenotypic differences between patients with the same imbalance within a family. In some {open_quotes}restrictive{close_quotes} combinations the abnormal embryos will die, although in {open_quotes}permissive{close_quotes} combinations they can survive. 47 refs., 2 figs., 3 tabs.

  20. Biometry of face and brain in fetuses with trisomy 21.

    Science.gov (United States)

    Guihard-Costa, Anne-Marie; Khung, Suonavy; Delbecque, Kathy; Ménez, Françoise; Delezoide, Anne-Lise

    2006-01-01

    The aim of this study was to specify the early setting of the particular craniofacial morphology in Down syndrome during the fetal period from data based on postmortem examinations. The study included 1277 fetuses at 15-38 gestational weeks (GW): 922 control fetuses and 355 fetuses with trisomy 21, selected from fetopathology units in Paris. Body weight (BW) and nine dimensions of the face, skull, and brain were recorded: the outer and inner canthal distances (OCD, ICD), biparietal diameter (BPD), head circumference (HC), brain weight (BrW), occipitofrontal diameters of left and right hemispheres (lOFD, rOFD), weight of the infratentorial part of the brain (IBW), and maximal transversal diameter of the cerebellum (CTD). Four ratios were computed: BPD/HC, OCD/BPD, BrW/BW, IBW/BrW. Differences between trisomic fetuses and control fetuses were tested by age interval. Results showed that BW, rOFD, and lOFD were lower in trisomic fetuses as early as 15 GW. Cerebellar hypoplasia included lower IBW and CTD in trisomic fetuses. The IBW/BrW ratio was higher in trisomic fetuses, showing that growth restriction affected the infratentorial part of the brain less than the supratentorial part. Early brachycephaly was found in trisomic fetuses, with higher values of BPD and BPD/HC from 15 GW. ICD and OCD were not significantly different in the two groups, but OCD/DBP ratio was lower in trisomic fetuses. These results confirm the early phenotypical expression of trisomy 21 on craniofacial morphology, associated with a marked restriction of brain growth, especially in the supratentorial part. PMID:16326987

  1. 无创产前基因测序在胎儿染色体非整倍体基因检测中的临床应用%The application of non-invasive prenatal genetic sequencing for fetal chromosomal aneuploidy

    Institute of Scientific and Technical Information of China (English)

    翁慧男; 梁嘉颖; 曾伟宏; 汤惠霞; 孙怡; 马将军

    2015-01-01

    1 to January 2013 were selected.Inclusion criteria:advanced age,prenatal screening for high risk,and fetal abnormality indicated by color ultrasonography,agreeing with non-invasive prenatal genetic testing.After non-invasive prenatal genetic testing, the pregnant women with positive result underwent cell culture and chromosomal karyotyping.Following the situations after deliv-ery were designed as the final criteria for definite diagnosis of fetal chromosomal aneuploidy.Results A total of 1 865 pregnant women underwent non-invasive prenatal genetic testing,of which 21 pregnant women were found with positive result,including 14 pregnant women with trisomy 21,5 pregnant women with trisomy 18,2 pregnant women with trisomy 13.The results of chromo-somal karyotyping after amniocentesis or umbilical cord blood puncture were designed as golden standard.Among the women with trisomy 21,one woman refused the prenatal diagnosis,self induced labor and could not be confirmed karyotype.No false positive case was found among the women with trisomy 18 and 13.No missed diagnosis was found among the pregnant women with negative result during follow-up after delivery.Through statistical analysis of non-invasive prenatal fetal genetic testing,the sensitivity for the trisomy 21 was 100%,and the accuracy was 92.9%.The sensitivity and accuracy for the trisomy 18 and 13 were 100%.Conclu-sion Non-invasive prenatal genetic testing can improve the diagnostic efficacy before delivery,reduce the birth of ill infants,and it is a quick,safe,easy-accepted and reliable prenatal diagnostic method,which is worthy to be popularized and an inexorable trend of development in the future.

  2. Altered DNA methylation in leukocytes with trisomy 21.

    Directory of Open Access Journals (Sweden)

    Kristi Kerkel

    2010-11-01

    Full Text Available The primary abnormality in Down syndrome (DS, trisomy 21, is well known; but how this chromosomal gain produces the complex DS phenotype, including immune system defects, is not well understood. We profiled DNA methylation in total peripheral blood leukocytes (PBL and T-lymphocytes from adults with DS and normal controls and found gene-specific abnormalities of CpG methylation in DS, with many of the differentially methylated genes having known or predicted roles in lymphocyte development and function. Validation of the microarray data by bisulfite sequencing and methylation-sensitive Pyrosequencing (MS-Pyroseq confirmed strong differences in methylation (p<0.0001 for each of 8 genes tested: TMEM131, TCF7, CD3Z/CD247, SH3BP2, EIF4E, PLD6, SUMO3, and CPT1B, in DS versus control PBL. In addition, we validated differential methylation of NOD2/CARD15 by bisulfite sequencing in DS versus control T-cells. The differentially methylated genes were found on various autosomes, with no enrichment on chromosome 21. Differences in methylation were generally stable in a given individual, remained significant after adjusting for age, and were not due to altered cell counts. Some but not all of the differentially methylated genes showed different mean mRNA expression in DS versus control PBL; and the altered expression of 5 of these genes, TMEM131, TCF7, CD3Z, NOD2, and NPDC1, was recapitulated by exposing normal lymphocytes to the demethylating drug 5-aza-2'deoxycytidine (5aza-dC plus mitogens. We conclude that altered gene-specific DNA methylation is a recurrent and functionally relevant downstream response to trisomy 21 in human cells.

  3. A contemporary, single-institutional experience of surgical versus expectant management of congenital heart disease in trisomy 13 and 18 patients.

    Science.gov (United States)

    Costello, John P; Weiderhold, Allison; Louis, Clauden; Shaughnessy, Conner; Peer, Syed M; Zurakowski, David; Jonas, Richard A; Nath, Dilip S

    2015-06-01

    The objective of this study was to examine a large institutional experience of patients with trisomy 13 and trisomy 18 in the setting of comorbid congenital heart disease and present the outcomes of surgical versus expectant management. It is a retrospective single-institution cohort study. Institutional review board approved this study. Thirteen consecutive trisomy 18 patients and three consecutive trisomy 13 patients (sixteen patients in total) with comorbid congenital heart disease who were evaluated by our institution's Division of Cardiovascular Surgery between January 2008 and December 2013 were included in the study. The primary outcome measures evaluated were operative mortality (for patients who received surgical management), overall mortality (for patients who received expectant management), and total length of survival during follow-up. Of the thirteen trisomy 18 patients, seven underwent surgical management and six received expectant management. With surgical management, operative mortality was 29 %, and 80 % of patients were alive after a median follow-up of 116 days. With expectant management, 50 % of patients died before hospital discharge. Of the three patients with trisomy 13, one patient underwent surgical management and two received expectant management. The patient who received surgical management with complete repair was alive at last follow-up over 2 years after surgery; both patients managed expectantly died before hospital discharge. Trisomy 13 and trisomy 18 patients with comorbid congenital heart disease can undergo successful cardiac surgical intervention. In this population, we advocate that nearly all patients with cardiovascular indications for operative congenital heart disease intervention should be offered complete surgical repair over palliative approaches for moderately complex congenital cardiac anomalies.

  4. Partial trisomy 21: a fifty-year follow-up visit.

    Science.gov (United States)

    Hamm, J Austin; Carroll, Andrew J; Mikhail, Fady M; Korf, Bruce R; Finley, Wayne H

    2015-07-01

    We describe a clinical encounter with family members that carry a balanced translocation involving chromosomes 15 and 21 roughly 50 years after the proband was diagnosed with partial trisomy 21 due to an unbalanced translocation. We discuss how these chromosomal rearrangements have impacted the lives of these individuals, and how they responded to revisiting their diagnoses after using updated cytogenetic techniques including high resolution chromosome banding and array comparative genomic hybridization. PMID:25944586

  5. Value of quantitative fluorescent polymerase chain reaction in the rapid prenatal diagnosis of common chromosomal aneuploidies%QF-PCR快速产前诊断常见非整倍体病的价值

    Institute of Scientific and Technical Information of China (English)

    纪妍; 朱津; 卢燕

    2016-01-01

    Objective To explore the value of quantitative fluorescent-polymerase chain reaction (QF-PCR) in the prenatal diagnosis of common chromosomal aneuploidies. Methods A total of 1 035 pregnant women received pre-natal diagnosis in our hospital from January 2013 to June 2014 were selected, which were all tested by karyotype analy-sis and QF-PCR. The results of the two methods were compared. Results Among the 1 008 cases that were normal by karyotype analysis, 4 were abnormal in QF-PCR, in which 1 was proved to be normal by follow-up and 3 were proved to be normal by short tandem report (STR). Eighteen cases were diagnosed as abnormal involving chromosome 21, 18, 13, X and Y both by karyotype analysis and QF-PCR, including 1 case of trisomy mosaicism 18 and 1 cases of transloca-tion trisomy 21. The coincidence rate was 100%. Conclusion QF-PCR could provide rapid and effective diagnosis for chromosomal aneuploidies, but misdiagnosis may still occur. The appropriate STR combination can improve the detec-tion efficiency. It is an efficient and reliable method for rapid prenatal diagnosis, which provides an important supple-ment for karyotype analysis.%目的 评价荧光定量聚合酶链反应(OF-PCR)技术在产前快速诊断常见染色体非整倍体病的临床价值.方法 选取2013年1月至2014年6月在我院进行产前诊断的孕妇1 035例,所有孕妇均接受染色体核型分析及QF-PCR检查,比较并分析两种检验结果的符合性.结果 染色体核型分析正常的孕妇1 008例中有4例QF-PCR怀疑异常,其中3例经增加短串联重复序列(STR)位点再次分析,结果正常,1例随访未见异常.18例21、18、13、X、Y染色体非整倍体两者结果一致(包括1例18三体嵌合体及1例易位型21-三体),符合率为100%.结论 QF-PCR能快速高效的检出染色体非整倍体,但仍有误诊可能,选择适宜的STR组合可以提高检测效率,QF-PCR作为染色体核型分析的有效补充在快速产前诊断中有重要价值.

  6. Cell-free fetal DNA and cell-free total DNA levels in spontaneous abortion with fetal chromosomal aneuploidy.

    Directory of Open Access Journals (Sweden)

    Ji Hyae Lim

    Full Text Available BACKGROUND: Cell-free fetal DNA and cell-free total DNA in maternal circulation have been proposed as potential markers for noninvasive monitoring of the placental condition during the pregnancy. However, the correlation of and change in cell-free fetal DNA and cell-free total DNA in spontaneous abortion (SA with fetal chromosomal aneuploidy have not yet been reported. Therefore, we investigated cell-free fetal DNA and cell-free total DNA levels in SA women with fetal chromosomal aneuploidy. METHODOLOGY/PRINCIPAL FINDINGS: A nested case-control study was conducted with maternal plasma collected from 268 women in their first trimester of pregnancy. Subjects included 41 SA with normal fetal karyotype, 26 SA with fetal chromosomal aneuploidy, and 201 normal controls. The unmethylated PDE9A gene was used to measure the maternal plasma levels of cell-free fetal DNA. The GAPDH gene was used to measure the maternal plasma levels of cell-free total DNA. The diagnostic accuracy was measured using receiver-operating characteristic (ROC curves. Levels of cell-free fetal DNA and cell-free total DNA were significantly higher in both SA women with normal fetal karyotype and SA women with fetal chromosomal aneuploidy in comparison with the normal controls (P<0.001 in both. The correlation between cell-free fetal DNA and cell-free total DNA levels was stronger in the normal controls (r = 0.843, P<0.001 than in SA women with normal karyotype (r = 0.465, P = 0.002 and SA women with fetal chromosomal aneuploidy (r = 0.412, P = 0.037. The area under the ROC curve for cell-free fetal DNA and cell-free total DNA was 0.898 (95% CI, 0.852-0.945 and 0.939 (95% CI, 0.903-0.975, respectively. CONCLUSIONS: Significantly high levels of cell-free fetal DNA and cell-free total DNA were found in SA women with fetal chromosomal aneuploidy. Our findings suggest that cell-free fetal DNA and cell-free total DNA may be useful biomarkers for the prediction of SA

  7. Host-induced aneuploidy and phenotypic diversification in the Sudden Oak Death pathogen Phytophthora ramorum

    Science.gov (United States)

    Aneuploidy can result in significant phenotypic changes, which can sometimes be selectively advantageous. For example, aneuploidy confers resistance to antifungal drugs in human pathogenic fungi. Aneuploidy has also been observed in invasive fungal and oomycete plant pathogens in the field. Environm...

  8. Patau syndrome with long survival in a case of unusual mosaic trisomy 13.

    Science.gov (United States)

    Fogu, Giuseppina; Maserati, Emanuela; Cambosu, Francesca; Moro, Maria Antonietta; Poddie, Fausto; Soro, Giovanna; Bandiera, Pasquale; Serra, Gigliola; Tusacciu, Gianni; Sanna, Giuseppina; Mazzarello, Vittorio; Montella, Andrea

    2008-01-01

    We report a 12-year-old patient with Patau syndrome, in whom two cell lines were present from birth, one with total trisomy 13 due to isochromosome (13q), and one with partial trisomy 13. A cytogenetic re-evaluation at 9 years of age brought to light in skin fibroblasts a third cell line, partially monosomic for chromosome 13. The derivatives (13) present in the three cell lines were characterized through fluorescence in situ hybridization (FISH) experiments with suitable probes; the results suggested a sequence of rearrangements which beginning from an isochromosome (13q) could have led to the other two derivatives. We report the clinical data at birth and at the age of 12; at this age pigmentary lesions with phylloid pattern were noted. Cytogenetic findings of the chromosomal analyses on different tissues, including skin fibroblasts from differently pigmented areas, are also reported. PMID:18495567

  9. Prenatal diagnosis of an autosomal translocation with regular trisomy 21.

    Science.gov (United States)

    Tunca, Yusuf; Deveci, M Salih; Koc, Altug; Kaya, Halide; Alanbay, Ibrahim; Coksuer, Hakan; Dede, Murat

    2013-06-01

    The coincidence of trisomy 21 and a structural rearrangement is very rare, and even it has not been reported as a prenatal diagnosis yet. In this article, we present an autosomal translocation carrier fetus with trisomy 21: 47,XX,+21, t(3;8)(p21;q24). Although the coincidence of reciprocal translocation and trisomy may be seen in reciprocal translocation carrier families, de novo cases are extremely rare. The presented case is diagnosed by amniocentesis, which was performed because of abnormal fetal ultrasonographic findings and increased trisomy 21 risk at maternal serum screening test. The postmortem pathologic examination of the fetus revealed that the findings of hypertelorism and right lung with two lobes are interesting novel findings of our cases associated with the breakpoints 3p21 and 8q24.

  10. Holoprosencephaly with caudal dysplasia. Pseudo-trisomy 13 or a distinct entity?

    Energy Technology Data Exchange (ETDEWEB)

    Hicks, R.P.B.; Aylsworth, A.S. [Univ. of North Carolina at Chapel Hill, Durham, NC (United States); Timmons, M.C. [Duke Univ. Medical Center, Durham, NC (United States)

    1994-09-01

    We have studied three chromosomally normal patients with multiple anomalies that include holoprosencephaly and caudal dysplasia. Each has features found in patients with pseudo-trisomy 13, though each lacks malformations common in that syndrome. Patients 1 and 2 did not have polydactyly and patients 2 and 3 had no congenital heart malformation. Patient 1 is also unusual in that he does not have typical holoprosencephalic facies and is alive at age 25 months. We have also identified two other similar patients in the London Dysmorphology Database, each of which had holoprosencephaly, congenital heart malformation, and imperforate anus. Isolated caudal dysplasia and holoprosencephaly are both causally heterogeneous. They have been reported together rarely in patients with several different syndromes including chromosomal abnormalities, monogenic syndromes, teratogenic insults, and syndromes of unknown cause. Over thirty cases of {open_quotes}pseudo-trisomy 13{close_quotes} have now been reported and eight of these have had features of caudal dysplasia. There have been four with imperforate anus or anal stenosis, one with lumbosacral vertebral anomaly, and three others with bilateral renal agenesis or hypoplasia. Based on our patients and this review of other reported and unreported cases, we suggest that caudal dysplasia may be a significant clinical feature of pseudo-trisomy 13. Alternatively, holoprosencephaly and caudal dysplasia with a normal karyotype may represent a similar though distinct entity. Some may have submicroscopic chromosomal deletions. Molecular studies of regions known to be associated with holoprosencephaly are currently in progress on tissue from Patient 1. We hope these observations will stimulate reports of similarly affected patients to allow better definition of pseudo-trisomy 13 and other overlap syndromes.

  11. Partial trisomy 11q involving chromosome 1 detected by fluorescence in situ hybridization

    Energy Technology Data Exchange (ETDEWEB)

    McCorquodale, M.; Bereziouk, O.; McCorquodale, D.J. [Univ. of Illinois College of Medicine, Chicago, IL (United States)] [and others

    1994-09-01

    Partial trisomy 11q was detected in an infant delivered 3-4 weeks prematurely. The phenotype included slanted palpebral fissures, high arched palate, developmental delay, microcephaly, and cardiac defects, all of which occur in the majority of cases with this syndrome. Other features included a column-shaped skull, preauricular pit, single palmar crease, short, broad great toes, flat occiput, unilateral kidney agenesis, and strabismus. Chromosomes obtained from peripheral blood cells revealed the presence of extra material on the long arm of chromosome 1. The G-banding pattern of this extra material indicated that it might be derived from chromosome 1 or 11. Chromosomal {open_quotes}paints{close_quotes} showed that it was not chromosome 1 material, but was chromosome 11 material extending from band q21 to qter. Partial trisomy 11q arising from translocation of the 11q material to chromosome 2, 3, 4, 5, 6, 9, 10, 13, 17, 21, 22, and X has been reported previously, whereas translocation to chromosome 1 has not. The chromosome to which the 11q material is translocated does not alter the most frequent features of the partial trisomy 11q syndrome, but may influence other less common features.

  12. TRISOMY 18 in a 50-year-old female

    Directory of Open Access Journals (Sweden)

    Bhanumathi B

    2006-01-01

    Full Text Available She was brought to our Institute at the age of 31, with speech delay and mental handicap. She was assessed by the multidisciplinary team in the institute to determine the cause of her problems. Clinical evaluation revealed dysmorphic facial features, microbrachycephaly, camptodactyly, clinodactyly, abnormal dermatoglyphics and severe mental handicap. Cardiovascular system examination was normal. Chromosomal analysis revealed a trisomy of Chromosome 18. The phenotype of trisomy 18 and the rarity of prolonged survival in this case are discussed.

  13. Overexpression of esterase D in kidney from trisomy 13 fetuses.

    OpenAIRE

    Loughna, S; P. Bennett; Gau, G; K. Nicolaides; Blunt, S; Moore, G

    1993-01-01

    Human trisomy 13 (Patau syndrome) occurs in approximately 1 in 5,000 live births. It is compatible with life, but prolonged survival is rare. Anomalies often involve the urogenital, cardiac, craniofacial, and central nervous systems. It is possible that these abnormalities may be due to the overexpression of developmentally important genes on chromosome 13. The expression of esterase D (localized to chromosome 13q14.11) has been investigated in both muscle and kidney from trisomy 13 fetuses a...

  14. An infant with double trisomy (48,XXX,+18)

    Energy Technology Data Exchange (ETDEWEB)

    Jaruratanasirikul, S.; Jinorose, U. [Prince of Songkla Univ. (Thailand)

    1994-01-15

    The authors report on an infant with double trisomy 48,XXX,+18. She presented with manifestation of trisomy 18: prominent occiput, microphthalmia, small mouth, micrognathia, malformed ears, congenital heart defect, overlapping fingers, talipes equinovarus, and rockerbottom feet. An extra palmar crease was present only on the right hand. This patient was alive at 12 months. The clinical manifestations are compared with those of 10 previously reported cases. 13 refs., 3 figs., 1 tab.

  15. Cell-free DNA screening and sex chromosome aneuploidies.

    Science.gov (United States)

    Mennuti, Michael T; Chandrasekaran, Suchitra; Khalek, Nahla; Dugoff, Lorraine

    2015-10-01

    Cell-free DNA (cfDNA) testing is increasingly being used to screen pregnant women for fetal aneuploidies. This technology may also identify fetal sex and can be used to screen for sex chromosome aneuploidies (SCAs). Physicians offering this screening will need to be prepared to offer comprehensive prenatal counseling about these disorders to an increasing number of patients. The purpose of this article is to consider the source of information to use for counseling, factors in parental decision-making, and the performance characteristics of cfDNA testing in screening for SCAs. Discordance between ultrasound examination and cfDNA results regarding fetal sex is also discussed.

  16. Natural histroy of trisomy 18 and trisomy 13: I. Growth, physical assessment, medical histories, survival, and recurrence risk

    Energy Technology Data Exchange (ETDEWEB)

    Baty, B.J.; Blackburn, B.L.; Carey, J.C. [Univ. of Utah School of Medicine, Salt Lake City, UT (United States)

    1994-01-15

    The natural history of trisomy 18 and trisomy 13 was investigated using data derived from parent questionnaires and medical records from 98 families with an index case of trisomy 18 and 32 families with an index case of trisomy 13. Data are presented on pregnancy, delivery, survival, medical complications, immunizations, growth, cause of death, cytogenetics, and recurrence risk. Half of the trisomy 18 babies were delivered by C-section. Fetal distress was a factor in half, and the only reason in a third of C-section deliveries. One minute Apgar scores were significantly lower in C-section and breech deliveries. There were more small-for-gestational-age babies than in the general population, but most of the low-birth-weight newborns were small for gestational age, unlike the general population. Survival in this group of children was better than in other studies due to ascertainment bias. There were more girls than boys at all ages for both conditions, and the sex ratio decreased with time. Growth curves for length, weight, head circumference, and weight vs height are provided. Long-term survival did not appear to be due to mosaicism. There were no adverse reactions attributable to immunizations. At age 1 year there was an average of approximately 2 operations per living child. The authors report the second case of successful major cardiac surgery in a trisomy 18 child. Almost 70% of deaths were attributed to cardiopulmonary arrest. The sibling recurrence risk for trisomy 18 or trisomy 13 was 0.55%. 86 refs., 5 figs., 5 tabs.

  17. Perspectives on the care and advances in the management of children with trisomy 13 and 18.

    Science.gov (United States)

    Carey, John C; Kosho, Tomoki

    2016-09-01

    The trisomy 13 and trisomy 18 syndromes are important and relatively common chromosome conditions each consisting of a recognizable pattern of multiple congenital anomalies, an increased neonatal and infant mortality, and a marked cognitive and motor disability in older children. Because of the medically serious nature of the outcomes, the traditional approach to management in the newborn and early infancy periods has been to withhold technological support and surgery. In the last decade a rich dialogue has emerged in the literature; one view makes the case for pure comfort care for the benefit of the child while the other view supports full intervention in appropriate situations. The principal aim of the series of articles in this issue of the Seminars in Medical Genetics is to enrich and continue this emerging dialogue. The papers include review articles, original research, and commentaries that discuss perspectives on the care and advances in the management of children with the trisomy 13 and 18 syndromes. © 2016 Wiley Periodicals, Inc. PMID:27643592

  18. Perspectives on the care and advances in the management of children with trisomy 13 and 18.

    Science.gov (United States)

    Carey, John C; Kosho, Tomoki

    2016-09-01

    The trisomy 13 and trisomy 18 syndromes are important and relatively common chromosome conditions each consisting of a recognizable pattern of multiple congenital anomalies, an increased neonatal and infant mortality, and a marked cognitive and motor disability in older children. Because of the medically serious nature of the outcomes, the traditional approach to management in the newborn and early infancy periods has been to withhold technological support and surgery. In the last decade a rich dialogue has emerged in the literature; one view makes the case for pure comfort care for the benefit of the child while the other view supports full intervention in appropriate situations. The principal aim of the series of articles in this issue of the Seminars in Medical Genetics is to enrich and continue this emerging dialogue. The papers include review articles, original research, and commentaries that discuss perspectives on the care and advances in the management of children with the trisomy 13 and 18 syndromes. © 2016 Wiley Periodicals, Inc.

  19. Atypical Down syndrome phenotype in a girl with 21;21 translocation trisomy.

    Science.gov (United States)

    Tuysuz, B; Yavuz, A; Ozdil, M; Caferler, J; Ozon, H

    2010-01-01

    We describe a girl with microcephaly, short stature, coarse face, severe growth and developmental delay, seizures, hypertonia, bilateral flexion contractures of the knees, and a de novo 21;21 translocation trisomy 21 in peripheral blood lymphocytes. Fluorescence in situ hybridization (FISH) analysis confirmed the trisomy 21 translocation using whole chromosome painting probe 21 (WCP21). Chromosome analysis which was also performed on skin fibroblasts and revealed mosaicism for a translocation trisomy 21 cell line (22.3%) as well as a second cell line consisting of one normal chromosome 21 and a small ring chromosome 21 derived from the translocation 21q21q (61%) and a third line consisting of monosomy 21 (16.7%). FISH analyses by LS121 probe for the critical (21q22.2-22.3) region of Down syndrome (DS) on interphase blood cells resulted with 30% two signals and 70% three signals, skin fibroblasts showed 84% single signal, 9% two signals and 7% three signals. The size of ring chromosome 21 in skin fibroblasts was very small and probably there was a large, more proximally located deletion including chromosome 21q22 band. We consider that the atypical DS phenotype of the patient originated from the small ring chromosome 21 and the monosomy 21 in the skin fibroblasts and other tissues not available for analysis. Therefore, the clinical findings of the patient were most similar to monosomy 21 mosaicism syndrome. PMID:20420031

  20. Heterozygosity for a Bub1 mutation causes female-specific germ cell aneuploidy in mice

    Energy Technology Data Exchange (ETDEWEB)

    Leland, Shawn; Nagarajan, Prabakaran; Polyzos, Aris; Thomas, Sharon; Samaan, George; Donnell, Robert; Marchetti, Francesco; Venkatachalam, Sundaresan

    2009-06-24

    Aneuploidy, the most common chromosomal abnormality at birth and the main ascertained cause of pregnancy loss in humans, originates primarily from chromosome segregation errors during oogenesis. Here we report that heterozygosity for a mutation in the mitotic checkpoint kinase gene, Bub1, induces aneuploidy in female germ cells of mice, and that the effect increases with advancing maternal age. Analysis of Bub1 heterozygous oocytes showed that aneuploidy occurred primarily during the first meiotic division and involved premature sister chromatid separation. Furthermore, aneuploidy was inherited in zygotes and resulted in the loss of embryos after implantation. The incidence of aneuploidy in zygotes was sufficient to explain the reduced litter size in matings with Bub1 heterozygous females. No effects were seen in germ cells from heterozygous males. These findings show that Bub1 dysfunction is linked to inherited aneuploidy in female germ cells and may contribute to the maternal age-related increase in aneuploidy and pregnancy loss.

  1. Opposite phenotypes of muscle strength and locomotor function in mouse models of partial trisomy and monosomy 21 for the proximal Hspa13-App region.

    Directory of Open Access Journals (Sweden)

    Véronique Brault

    2015-03-01

    Full Text Available The trisomy of human chromosome 21 (Hsa21, which causes Down syndrome (DS, is the most common viable human aneuploidy. In contrast to trisomy, the complete monosomy (M21 of Hsa21 is lethal, and only partial monosomy or mosaic monosomy of Hsa21 is seen. Both conditions lead to variable physiological abnormalities with constant intellectual disability, locomotor deficits, and altered muscle tone. To search for dosage-sensitive genes involved in DS and M21 phenotypes, we created two new mouse models: the Ts3Yah carrying a tandem duplication and the Ms3Yah carrying a deletion of the Hspa13-App interval syntenic with 21q11.2-q21.3. Here we report that the trisomy and the monosomy of this region alter locomotion, muscle strength, mass, and energetic balance. The expression profiling of skeletal muscles revealed global changes in the regulation of genes implicated in energetic metabolism, mitochondrial activity, and biogenesis. These genes are downregulated in Ts3Yah mice and upregulated in Ms3Yah mice. The shift in skeletal muscle metabolism correlates with a change in mitochondrial proliferation without an alteration in the respiratory function. However, the reactive oxygen species (ROS production from mitochondrial complex I decreased in Ms3Yah mice, while the membrane permeability of Ts3Yah mitochondria slightly increased. Thus, we demonstrated how the Hspa13-App interval controls metabolic and mitochondrial phenotypes in muscles certainly as a consequence of change in dose of Gabpa, Nrip1, and Atp5j. Our results indicate that the copy number variation in the Hspa13-App region has a peripheral impact on locomotor activity by altering muscle function.

  2. Numerically abnormal chromosome constitutions in humans

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1993-12-31

    Chapter 24, discusses numerically abnormal chromosome constitutions in humans. This involves abnormalities of human chromosome number, including polyploidy (when the number of sets of chromosomes increases) and aneuploidy (when the number of individual normal chromosomes changes). Chapter sections discuss the following chromosomal abnormalities: human triploids, imprinting and uniparental disomy, human tetraploids, hydatidiform moles, anomalies caused by chromosomal imbalance, 13 trisomy (D{sub 1} trisomy, Patau syndrome), 21 trisomy (Down syndrome), 18 trisomy syndrome (Edwards syndrome), other autosomal aneuploidy syndromes, and spontaneous abortions. The chapter concludes with remarks on the nonrandom participation of chromosomes in trisomy. 69 refs., 3 figs., 4 tabs.

  3. Molecular diagnostic testing for Klinefelter syndrome and other male sex chromosome aneuploidies

    Directory of Open Access Journals (Sweden)

    Hager Karl

    2012-04-01

    Full Text Available Abstract Background Male sex chromosome aneuploidies are underdiagnosed despite concomitant physical and behavioral manifestations. Objective To develop a non-invasive, rapid and high-throughput molecular diagnostic assay for detection of male sex chromosome aneuploidies, including 47,XXY (Klinefelter, 47,XYY, 48,XXYY and 48,XXXY syndromes. Methods The assay utilizes three XYM and four XA markers to interrogate Y:X and X:autosome ratios, respectively. The seven markers were PCR amplified using genomic DNA isolated from a cohort of 323 males with aneuploid (n = 117 and 46,XY (n = 206 karyotypes. The resulting PCR products were subjected to Pyrosequencing, a quantitative DNA sequencing method. Results Receiver operator characteristic (ROC curves were used to establish thresholds for the discrimination of aneuploid from normal samples. The XYM markers permitted the identification of 47,XXY, 48,XXXY and 47,XYY syndromes with 100% sensitivity and specificity in both purified DNA and buccal swab samples. The 48,XXYY karyotype was delineated by XA marker data from 46,XY; an X allele threshold of 43% also permitted detection of 48,XXYY with 100% sensitivity and specificity. Analysis of X chromosome-specific biallelic SNPs demonstrated that 43 of 45 individuals (96% with 48,XXYY karyotype had two distinct X chromosomes, while 2 (4% had a duplicate X, providing evidence that 48,XXYY may result from nondisjunction during early mitotic divisions of a 46,XY embryo. Conclusions Quantitative Pyrosequencing, with high-throughput potential, can detect male sex chromosome aneuploidies with 100% sensitivity.

  4. Trisomy 15 in a case of pediatric hemangiopericytoma and review of the literature.

    Science.gov (United States)

    Vadlamani, Indira; Ma, En; Brink, David S; Batanian, Jacqueline R

    2002-10-15

    This study reports on a pediatric case of hemangiopericytoma (HPC) showing trisomy 15 as a sole anomaly. Trisomy 15 was observed in a total of 11 cells harvested at a very early passage from two different in-situ cultures. Trisomy 15, as a sole anomaly, has been described in hematologic disorders such as myelodysplastic syndromes but, to our knowledge, has never been documented in solid tumors. This is the first report of HPC with trisomy 15. PMID:12505255

  5. Prenatal detection of microtia by MRI in a fetus with trisomy 22

    Energy Technology Data Exchange (ETDEWEB)

    Milic, Andrea; Blaser, Susan; Robinson, Ashley [University of Toronto, Department of Diagnostic Imaging, Hospital for Sick Children, Toronto (Canada); Viero, Sandra; Halliday, William [University of Toronto, Laboratory Medicine and Pathobiology, Hospital for Sick Children, Toronto (Canada); Winsor, Elizabeth [University of Toronto, Department of Laboratory Medicine and Pathobiology, Mount Sinai Hospital, Toronto (Canada); Toi, Ants [University of Toronto, Department of Diagnostic Imaging, Mount Sinai Hospital, Toronto (Canada); Thomas, Micki [University of Toronto, The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, Rm. 3292 Toronto, ON (Canada); Chitayat, David [University of Toronto, The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, Rm. 3292 Toronto, ON (Canada); University of Toronto, Clinical and Metabolic Genetics, Hospital for Sick Children, Toronto (Canada)

    2006-07-15

    Trisomy 22 is a rare chromosomal abnormality infrequently detected prenatally. External ear abnormalities, in particular microtia, are often associated with trisomy 22, but prenatal detection of microtia has not been reported in association with trisomy 22. We report a fetus with trisomy 22, with fetal MRI findings of microtia, craniofacial dysmorphism, and polygyria. Fetal MRI is a useful tool for auricular assessment and might have utility in the prenatal detection of chromosomal abnormalities, especially among fetuses with structural anomalies. (orig.)

  6. The relationship of maternal age and trisomy among trisomic spontaneous abortions.

    OpenAIRE

    Hassold, T; Warburton, D; Kline, J.; Stein, Z

    1984-01-01

    The relationship between maternal age and trisomy was examined by comparing mean ages of 954 trisomic spontaneous abortions with those of live births ascertained at the same study center. The overall mean for trisomy was highly significantly elevated over that of the newborns. The age effect was most pronounced for trisomies involving the small chromosomes, with trisomies 13, 14, 15, 16, 17, 18, 20, 21, and 22 all having significantly increased ages by comparison with the control population. ...

  7. First-trimester screening for trisomy 21 in Denmark: implications for detection and birth rates of trisomy 18 and trisomy 13

    DEFF Research Database (Denmark)

    Ekelund, C K; Petersen, Ole; Skibsted, Leif Horsfelt;

    2011-01-01

    In Denmark a new national guideline for prenatal screening and diagnosis was issued in 2004 according to which all pregnant women should be offered a first-trimester combined risk assessment for trisomy 21 (T21). The aim of this study was to investigate whether the new screening strategy for T21 ...

  8. Trisomy 13 and 18: Selecting the road previously not taken.

    Science.gov (United States)

    McCaffrey, Martin J

    2016-09-01

    The care of patients with trisomy 13 and 18 is a source of significant controversy. While these conditions are life limiting, indisputable data refutes the notion that these conditions are lethal or incompatible with life. Despite such evidence, arguments of beneficence, quality of life and limited resources are invoked to make the case to limit care to trisomy children. Lessons learned in our ignominious history with Down syndrome should guide us as we explore care for patients with trisomy 13 and 18. As clinicians we should strive with equipoise to carefully examine available data, the current status of practices related to care from palliation to intensive interventions, rise above our personal prejudices and listen to the voices of families imploring us to consider their opinions regarding the value of the life of a child with trisomy 13 or 18. We should recall and learn from our Down syndrome odyssey and select the road previously not taken as we chart a course to the best possible care for our trisomy 13 and 18 sisters and brothers. © 2016 Wiley Periodicals, Inc. PMID:27519759

  9. The risk of fetal loss following a prenatal diagnosis of trisomy 13 or trisomy 18.

    Science.gov (United States)

    Morris, Joan K; Savva, George M

    2008-04-01

    The objective of this study is to determine the risk of fetal loss (spontaneous abortion or stillbirth) following a prenatal diagnosis of trisomy 13 (T13; Patau syndrome) or trisomy 18 (T18; Edwards syndrome). Five regional congenital anomaly registers in England and Wales provided details on the outcomes of 198 pregnancies prenatally diagnosed with T13 and 538 prenatally diagnosed with T18. For each pregnancy the time from prenatal diagnosis until birth, miscarriage or termination occurred was calculated and these times were analyzed using Kaplan-Meier survival functions. Our results showed that between 12 weeks gestation and term an estimated 49% (95% CI: 29-73%) of pregnancies diagnosed with T13 and 72% (61-81%) of pregnancies diagnosed with T18 ended in a miscarriage or stillbirth. Between 18 weeks and term the proportions were 42% (18-72%) for T13 and 65% (57-79%) for T18 and between 24 weeks and term the proportions were 35% (5-70%) for T13 and 59% (49-77%) for T18. Male fetuses with T18 appeared to be more likely to be lost than female fetuses. These are the most precise estimates currently available for the risk of loss in a general population. These estimates should be useful in counseling women who are carrying an affected fetus and knowing the risk of fetal loss is essential to compare the performance of prenatal screening programs occurring in the first and second trimester. PMID:18361449

  10. Unexplained False Negative Results in Noninvasive Prenatal Testing : Two Cases Involving Trisomies 13 and 18

    NARCIS (Netherlands)

    Hochstenbach, R; Page-Christiaens, G C M L; van Oppen, A C C; Lichtenbelt, K D; van Harssel, J J T; Brouwer, T; Manten, G T R; van Zon, P; Elferink, M; Kusters, K; Akkermans, O; Ploos van Amstel, J K; Schuring-Blom, G H

    2015-01-01

    Noninvasive prenatal testing (NIPT) validation studies show high sensitivity and specificity for detection of trisomies 13, 18, and 21. False negative cases have rarely been reported. We describe a false negative case of trisomy 13 and another of trisomy 18 in which NIPT was commercially marketed di

  11. Illumina测序技术在母血检测胎儿非整倍体中应用%Detecting fetal chromosomal aneuploidy by Illumina-solexa sequencing DNA in maternal plasma

    Institute of Scientific and Technical Information of China (English)

    冯穗华; 张红云; 陈建勇; 王威; 黄泳华; 陈芳; 蒋馥蔓; 李卫凯; 麦巧娇; 瞿京辉; 张燕玲

    2012-01-01

    目的 研究Illumina测序技术在母血中检测胎儿非整倍体的可行性,及其在无创性产前诊断中的应用前景.方法 68例孕12-39周具有产前诊断指征的单胎妊娠孕妇抽取外周血进行离心、提取血浆中游离DNA,运用Illumina Hiseq2000测序技术进行DNA测序及统计分析.结果 68例孕妇通过Illumina测序技术检测出3例21三体,2例18三体、1例13三体及1例47,XYY.因为濒死胎儿羊水脱落细胞活力极低而致羊水培养失败,传统型染色体核型分析未检测出1例21三体.结论 Illumina测序作为一种无创性产前诊断技术,可准确地筛查21、18、13、X、Y等染色体非整倍体异常,具有安全、准确率高及假阳性率低的优点,值得临床推广.%Objective To study the feasibility of detecting fetal chromosomal aneuploidy and the perspective of non invasive prenatal diagnosis by Illumina sequencing DNA in maternal plasma. Methods 68 singleton pregnant women with gestation weeks of 12 — 39 were recruited. Maternal plasma DNA was extracted and sequenced on Illumina/ Hiseq2000 platform for subsequent statistics analysis. Results Three cases of trisomy 21,two cases of trisomy 18,one cases of trisomy 13,one cases of 47,XYY were successfully indentified by Illumina sequencing. One case of trisomy 21 wasn't detected in traditional karyotyping analysis because the cell of amniotic fluid had exceeding low vitality in the dying fetus. Conclusion As a kind technique of noninvasive prenatal diagnosis,Illumina sequencing Of maternal plasma DNA was effective in identifying fetal chromosomal aneuploidy such as 21,18,13,X,Y. Considering its accuracy and se curity,it Would be worth spreading in clinic.

  12. Trisomy of the Dscr1 gene suppresses early progression of pancreatic intraepithelial neoplasia driven by oncogenic Kras

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jang Choon; Shin, Jimin; Baek, Kwan-Hyuck, E-mail: khbaek@skku.edu

    2013-10-11

    Highlights: •A single extra copy of Dscr1 restrains progression of PanIN-1A to PanIN-1B lesions. •Dscr1 trisomy attenuates calcineurin–NFAT pathway in neoplastic ductal epithelium. •Dscr1 trisomy leads to upregulation of p15{sup INK4b} in neoplastic ductal epithelium. •A single extra copy of Dscr1 reduces epithelial proliferation in early PanIN lesions. •Dscr1 trisomy may protect Down syndrome individuals from pancreatic cancer. -- Abstract: Individuals with Down syndrome exhibit remarkably reduced incidence of most solid tumors including pancreatic cancer. Multiple mechanisms arising from the genetic complexity underlying Down syndrome has been suggested to contribute to such a broad cancer protection. In this study, utilizing a genetically engineered mouse model of pancreatic cancer, we demonstrate that trisomy of the Down syndrome critical region-1 (Dscr1), an endogenous calcineurin inhibitor localized on chromosome 21, suppresses the progression of pancreatic intraepithelial neoplasia-1A (PanIN-1A) to PanIN-1B lesions without affecting the initiation of PanIN lesions mediated by oncogenic Kras{sup G12D}. In addition, we show that Dscr1 trisomy attenuates nuclear localization of nuclear factor of activated T-cells (NFAT) accompanied by upregulation of the p15{sup Ink4b} tumor suppressor and reduction of cell proliferation in early PanIN lesions. Our data suggest that attenuation of calcineurin–NFAT signaling in neoplastic pancreatic ductal epithelium by a single extra copy of Dscr1 is sufficient to inhibit the progression of early PanIN lesions driven by oncogenic Kras, and thus may be a potential mechanism underlying reduced incidence of pancreatic cancer in Down syndrome individuals.

  13. Establishment of a 10-Plex Quantitative Fluorescent-PCR Assay for rapid diagnosis of sex chromosome aneuploidies.

    Science.gov (United States)

    Xie, Xingmei; Liang, Qiaoyi

    2014-01-01

    Sex chromosome aneuploidies occur commonly in the general population, with an incidence of 1 in 400 newborns. However, no tests specifically targeting sex chromosomes have been carried out in prenatal diagnosis or newborn screening, resulting in late recognition of these diseases. In this study, a rapid diagnostic method for sex chromosome aneuploidies was established using Quantitative Fluorescent-PCR (QF-PCR). Ten markers were included in one multiplex QF-PCR assay, including two sex determination genes (AMXY and SRY), five X-linked short tandem repeats (STRs; DXS1053, DXS981, DXS6809, DXS1187, and DXS8377), one X/Y-common STR (X22), and two autosomal STRs (D13S305 and D21S11). Retrospective tests of 70 cases with known cytogenetic results indicated that the 10-plex QF-PCR assay could well determine sex chromosome copy numbers by both allelic peak numbers and a sex chromosome dosage calculation with the autosomal STRs as internal controls. Prospective comparison with cytogenetic karyotyping on 534 cases confirmed that the 10-plex QF-PCR assay could be well employed for sex chromosome aneuploidy diagnosis in at least the Chinese Han population. This is the first QF-PCR test for the diagnosis of sex chromosome aneuploidies in the Chinese population. This test is superior to previous designs by including up to 8 sex-linked markers covering different parts of sex chromosomes as well as employing internal controls for copy number dosage calculation in a single PCR reaction. Due to simple technique and data analysis, as well as easy implementation within routine clinical services, this method is of great clinical application value and could be widely applied.

  14. Establishment of a 10-Plex Quantitative Fluorescent-PCR Assay for rapid diagnosis of sex chromosome aneuploidies.

    Directory of Open Access Journals (Sweden)

    Xingmei Xie

    Full Text Available Sex chromosome aneuploidies occur commonly in the general population, with an incidence of 1 in 400 newborns. However, no tests specifically targeting sex chromosomes have been carried out in prenatal diagnosis or newborn screening, resulting in late recognition of these diseases. In this study, a rapid diagnostic method for sex chromosome aneuploidies was established using Quantitative Fluorescent-PCR (QF-PCR. Ten markers were included in one multiplex QF-PCR assay, including two sex determination genes (AMXY and SRY, five X-linked short tandem repeats (STRs; DXS1053, DXS981, DXS6809, DXS1187, and DXS8377, one X/Y-common STR (X22, and two autosomal STRs (D13S305 and D21S11. Retrospective tests of 70 cases with known cytogenetic results indicated that the 10-plex QF-PCR assay could well determine sex chromosome copy numbers by both allelic peak numbers and a sex chromosome dosage calculation with the autosomal STRs as internal controls. Prospective comparison with cytogenetic karyotyping on 534 cases confirmed that the 10-plex QF-PCR assay could be well employed for sex chromosome aneuploidy diagnosis in at least the Chinese Han population. This is the first QF-PCR test for the diagnosis of sex chromosome aneuploidies in the Chinese population. This test is superior to previous designs by including up to 8 sex-linked markers covering different parts of sex chromosomes as well as employing internal controls for copy number dosage calculation in a single PCR reaction. Due to simple technique and data analysis, as well as easy implementation within routine clinical services, this method is of great clinical application value and could be widely applied.

  15. Noninvasive DNA testing technology in the application of the fetal chromosomal aneuploidy disease%无创DNA检测技术对胎儿染色体非整倍体疾病的筛查效果

    Institute of Scientific and Technical Information of China (English)

    马婷婷; 刘华平; 侯朝晖; 任东平

    2015-01-01

    -throughput sequencing technology to find out the risk rate of fetal suffering from fetal chromosomal aneuploidy diseases(such as Down's syndrome, Trisomy 18 syndrome, Trisomy 13 syndrome). Consultation was given to those whose detection results were at high risk, diagnostic means such as amniotic fluid puncture were suggested, and the pregnancy outcomes were followed up.Results We found a total of 23 cases of noninvasive prenatal detection of DNA abnormal: 10 cases suggested high risk of Down's syndrome, 2 cases suggested high risk of Trisomy 18 syndrome, 1 case suggested critical risk of Trisomy 18 syndrome, 3 cases suggested high risk of Trisomy 13 syndrome, 3 cases suggested sex chromosome abnormality(2 cases suggested 45,X0; 1 case suggested 47,XXY), 4 cases prompted other chromosomal abnormalities(2 cases suggested chromosome 7 bullish, 1 case of chromosome 16 bullish, 1 case of chromosome 17 bullish). Amniotic fluid puncture examination confirmed 11 cases of fetal chromosomal aneuploidy disease. 11 cases of confirmed fetal chromosomal aneuploidy disease contained 6 cases of Down's syndrome; 2 cases of Trisomy 18 syndrome; 2 cases of Trisomy 13 syndrome; 1 case of 47, XXY. 2 cases of noninvasive genetic tests prompted abnormal, but amniotic fluid puncture examination was normal, then byfollowing up their pregnancy outcomes, no abnormalities were found. The sensitivity of noninvasive prenatal detection of DNA technology in the diagnosis of chromosomal aneuploidy abnormality was 100%, the specificity was 99.81%, the false positive rate was 0.19%, and the false negative rate was 0%. Conclusion Noninvasive prenatal detection of DNA technology is noninvasive and accurate in screening for fetal chromosomal aneuploidy disease, having clinical value.

  16. Frontomaxillary Facial Angle Measurement in Screening for Trisomy 18 at 11 + 0 to 13 + 6 Weeks of Pregnancy: A Double-Centre Study

    Directory of Open Access Journals (Sweden)

    Bartosz Czuba

    2013-01-01

    Full Text Available Objective. The aim of this study was to evaluate the effectiveness of prenatal screening for trisomy 18 with the use of the frontomaxillary facial angle (FMF angle measurement. Material and Methods. The study involved 1751 singleton pregnancies at 11–13 + 6 weeks, examined between 2007 and 2011. Serum PAPP-A and free beta-hCG levels were assessed, and crown-rump length, nuchal translucency, and FMF angle were measured in all patients. 1350 fetuses with known follow-up were included in the final analysis. Results. Highly significant (P<0.01 negative correlation between the CRL and the FMF angle was found. There were 30 fetuses with trisomy 18. FMF angle was highly significantly larger (P<0.0001 in fetuses with trisomy 18 as compared to chromosomally normal fetuses. Two models of first trimester screening were compared: Model 1 based on maternal age, NT, and first trimester biochemistry test (DR 80–85% and FPR 0.3–0.6%, and Model 2 = Model 1 + FMF angle measurement (DR 87.3–93.3% and FPR 0.8–1.3%. Conclusions. The use of FMF angle measurement increases the effectiveness of the screening for trisomy 18. Introduction of the FMF angle as an independent marker for fetal trisomy 18 risk requires further prospective research in large populations.

  17. Overexpression of esterase D in kidney from trisomy 13 fetuses

    Energy Technology Data Exchange (ETDEWEB)

    Loughna, S.; Moore, G. (Institute of Obstetrics and Gynaecology, London (United Kingdom)); Gau, G.; Blunt, S. (Cytogenetics Lab., London (United Kingdom)); Nicolaides, K. (King' s College School of Medicine and Dentistry, London (United Kingdom))

    1993-10-01

    Human trisomy 13 (Patau syndrome) occurs in approximately 1 in 5,000 live births. It is compatible with life, but prolonged survival is rare. Anomalies often involve the urogenital, cardiac, craniofacial, and central nervous systems. It is possible that these abnormalities may be due to the overexpression of developmentally important genes on chromosome 13. The expression of esterase D (localized to chromosome 13q14.11) has been investigated in both muscle and kidney from trisomy 13 fetuses and has been compared with normal age- and sex-matched fetal tissues, by using northern analysis. More than a twofold increase in expression of esterase D was found in the kidney of two trisomy 13 fetuses, with normal levels in a third. Overexpression was not seen in the muscle tissues from these fetuses. 34 refs., 3 figs., 2 tabs.

  18. Correlation between induction of meiotic delay and aneuploidy in male mouse germ cells

    Energy Technology Data Exchange (ETDEWEB)

    Adler, I.D.; Gassner, P.; Schriever-Schwemmer, G.; Min, Zhou Ru [Institut fuer Sauugetiergenetik, Neuherberg (Germany)

    1993-12-31

    No aneuploidy assays are prescribed in any international guidelines for chemical safety testing up to now. The CEC-sponsored Aneuploidy Project has the aim to validate test methods for aneuploidy induction which could be used as screening tests. Furthermore, one of the major goals is to develop an understanding of mechanisms by which aneuploidy is induced. The present paper describes the investigation of meiotic delay and aneuploidy induction with the drug diazepam (DZ), the environmentally important mutagen acrylamide (AA) and the spindle poison colchicine (COL), which is used as a positive control. The time course of events was investigated. It is concluded that the assessment of meiotic delay can be used to preselect chemicals which require evaluation of aneuploidy induction during MMI in male germ cells.

  19. Prenatal ultrasonography of trisomy 18 with radial aplasia: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jee Young; Lee, Yeon Hee [Dankook University College of Medicine, Seoul (Korea, Republic of)

    2002-06-15

    Trisomy 18 (Edward syndrome) is the second most common chromosomal anomaly of the autosomal trisomy. Prenatal diagnosis of trisomy 18 is extremely important because of the complex malformations and lethal prognosis. Prenatal sonographic findings at 17 weeks of gestation showing radial aplasia with upper limb contracture, omphalocele, and suspicious esophageal atresia suggested the diagnosis and led to amniocentesis. Karyotyping revealed trisomy 18 (47 XX, +18, and characteristic autopsy findings were identified. We report a case of prenatally diagnosed trisomy 18 with a review of literatures.

  20. Limitations of Aneuploidy and Anomaly Detection in the Obese Patient

    Directory of Open Access Journals (Sweden)

    Paula Zozzaro-Smith

    2014-07-01

    Full Text Available Obesity is a worldwide epidemic and can have a profound effect on pregnancy risks. Obese patients tend to be older and are at increased risk for structural fetal anomalies and aneuploidy, making screening options critically important for these women. Failure rates for first-trimester nuchal translucency (NT screening increase with obesity, while the ability to detect soft-markers declines, limiting ultrasound-based screening options. Obesity also decreases the chances of completing the anatomy survey and increases the residual risk of undetected anomalies. Additionally, non-invasive prenatal testing (NIPT is less likely to provide an informative result in obese patients. Understanding the limitations and diagnostic accuracy of aneuploidy and anomaly screening in obese patients can help guide clinicians in counseling patients on the screening options.

  1. The epigenetic landscape of aneuploidy: constitutional mosaicism leading the way?

    Science.gov (United States)

    Davidsson, Josef

    2014-02-01

    The role of structural genetic changes in human disease has received substantial attention in recent decades, but surprisingly little is known about numerical chromosomal abnormalities, even though they have been recognized since the days of Boveri as partaking in different cellular pathophysiological processes such as cancer and genomic disorders. The current knowledge of the genetic and epigenetic consequences of aneuploidy is reviewed herein, with a special focus on using mosaic genetic syndromes to study the DNA methylation footprints and expressional effects associated with whole-chromosomal gains. Recent progress in understanding the debated role of aneuploidy as a driver or passenger in malignant transformation, as well as how the cell responds to and regulates excess genetic material in experimental settings, is also discussed in detail.

  2. Telomere DNA deficiency is associated with development of human embryonic aneuploidy.

    OpenAIRE

    Treff, Nathan R; Jing Su; Deanne Taylor; Scott, Richard T.

    2011-01-01

    Aneuploidy represents the most prevalent form of genetic instability found in human embryos and is the leading genetic cause of miscarriage and developmental delay in newborns. Telomere DNA deficiency is associated with genomic instability in somatic cells and may play a role in development of aneuploidy commonly found in female germ cells and human embryos. To test this hypothesis, we developed a method capable of quantifying telomere DNA in parallel with 24-chromosome aneuploidy screening f...

  3. Prediction model for aneuploidy in early human embryo development revealed by single-cell analysis

    Science.gov (United States)

    Vera-Rodriguez, Maria; Chavez, Shawn L.; Rubio, Carmen; Pera, Renee A. Reijo; Simon, Carlos

    2015-01-01

    Aneuploidies are prevalent in the human embryo and impair proper development, leading to cell cycle arrest. Recent advances in imaging and molecular and genetic analyses are postulated as promising strategies to unveil the mechanisms involved in aneuploidy generation. Here we combine time-lapse, complete chromosomal assessment and single-cell RT–qPCR to simultaneously obtain information from all cells that compose a human embryo until the approximately eight-cell stage (n=85). Our data indicate that the chromosomal status of aneuploid embryos (n=26), including those that are mosaic (n=3), correlates with significant differences in the duration of the first mitotic phase when compared with euploid embryos (n=28). Moreover, gene expression profiling suggests that a subset of genes is differentially expressed in aneuploid embryos during the first 30 h of development. Thus, we propose that the chromosomal fate of an embryo is likely determined as early as the pronuclear stage and may be predicted by a 12-gene transcriptomic signature. PMID:26151134

  4. Aneuploidy as a mechanism of adaptation to telomerase insufficiency.

    Science.gov (United States)

    Millet, Caroline; Makovets, Svetlana

    2016-08-01

    Cells' survival is determined by their ability to adapt to constantly changing environment. Adaptation responses involve global changes in transcription, translation, and posttranslational modifications of proteins. In recent years, karyotype changes in adapting populations of single cell organisms have been reported in a number of studies. More recently, we have described aneuploidy as an adaptation mechanism used by populations of budding yeast Saccharomyces cerevisiae to survive telomerase insufficiency induced by elevated growth temperature. Genetic evidence suggests that telomerase insufficiency is caused by decreased levels of the telomerase catalytic subunit Est2. Here, we present experiments arguing that the underlying cause of this phenomenon may be within the telomerase RNA TLC1: changes in the expression of TLC1 as well as mutations in the TLC1 template region affect telomere length equilibrium and the temperature threshold for the induction of telomerase insufficiency. We discuss what lies at the root of telomerase insufficiency, how cell populations overcome it through aneuploidy and whether reversible aneuploidy could be an adaptation mechanism for a variety of environmental stresses. PMID:26758992

  5. Aneuploidy as a mechanism for stress-induced liver adaptation.

    Science.gov (United States)

    Duncan, Andrew W; Hanlon Newell, Amy E; Bi, Weimin; Finegold, Milton J; Olson, Susan B; Beaudet, Arthur L; Grompe, Markus

    2012-09-01

    Over half of the mature hepatocytes in mice and humans are aneuploid and yet retain full ability to undergo mitosis. This observation has raised the question of whether this unusual somatic genetic variation evolved as an adaptive mechanism in response to hepatic injury. According to this model, hepatotoxic insults select for hepatocytes with specific numerical chromosome abnormalities, rendering them differentially resistant to injury. To test this hypothesis, we utilized a strain of mice heterozygous for a mutation in the homogentisic acid dioxygenase (Hgd) gene located on chromosome 16. Loss of the remaining Hgd allele protects from fumarylacetoacetate hydrolase (Fah) deficiency, a genetic liver disease model. When adult mice heterozygous for Hgd and lacking Fah were exposed to chronic liver damage, injury-resistant nodules consisting of Hgd-null hepatocytes rapidly emerged. To determine whether aneuploidy played a role in this phenomenon, array comparative genomic hybridization (aCGH) and metaphase karyotyping were performed. Strikingly, loss of chromosome 16 was dramatically enriched in all mice that became completely resistant to tyrosinemia-induced hepatic injury. The frequency of chromosome 16-specific aneuploidy was approximately 50%. This result indicates that selection of a specific aneuploid karyotype can result in the adaptation of hepatocytes to chronic liver injury. The extent to which aneuploidy promotes hepatic adaptation in humans remains under investigation.

  6. Chromosomal Instability, Aneuploidy, and Gene Mutations in Human Sporadic Colorectal Adenomas

    Directory of Open Access Journals (Sweden)

    Walter Giaretti

    2004-01-01

    Full Text Available Whether in vivo specific gene mutations lead to chromosomal instability (CIN and aneuploidy or viceversa is so far not proven. We hypothesized that aneuploidy among human sporadic colorectal adenomas and KRAS2 and APC mutations were not independent. Additionally, we investigated if 1p34–36 deletions by dual target FISH were associated with aneuploidy. Among 116 adenomas, 29 were DNA aneuploid by flow cytometry (25% and 29 were KRAS2 mutated (25%. KRAS2 mutations were associated with aneuploidy (P=0.02. However, while G–C and G–T transversions were strongly associated with DNA aneuploidy (P=0.007, G–A transitions were not. Within a second series of 61 adenomas, we found, instead, that APC mutational status and aneuploidy by flow cytometry were not associated. However, a statistically significant association was found with specific APC mutations, i.e., occurring in the mutation cluster region (MCR, codons 1200–1500 or downstream (P=0.016. Finally, the correlation of 1p34–36 deletions with flow cytometric and FISH detected aneuploidy was also significant (P=0.01. Specific KRAS2 and APC mutations and loss of genes in the 1p34–36 region appear associated with aneuploidy suggesting that these events are not independent and may cooperate in inducing human sporadic colorectal adenomas. A cause effect relationship between gene mutations and aneuploidy remains, however, to be demonstrated.

  7. The relationship between chemically-induced meiotic delay and aneuploidy in mouse oocytes and zygotes

    Energy Technology Data Exchange (ETDEWEB)

    Mailhes, J.B.; Marchetti, F. [Louisiana State Univ. Medical Center, Shreveport, LA (United States)

    1993-12-31

    Aneuploidy is a relatively common genetic disorder that results in human morbidity and mortality. Approximately 30% of embryonic and fetal deaths and 3.45 per thousand livebirths are associated with an abnormal number of chromosomes. Unfortunately, very little is known about the etiology and mechanism of chromosome missegregation. This situation dictates that considerable research be directed toward understanding the causes of aneuploidy. Although several hypotheses have been advanced for the etiology of aneuploidy, there still exists a paucity of information about the direct cuases and mechanisms of aneuploidy production. Without such specific knowledge, there is little hope of reducing the incidence of aneuploidy in humans. Some progress has been made. We now know that various chemicals can induce aneuploidy by interacting with certain cellular organelles, especially components of the spindle apparatus. These results have been demonstrated in various organisms and cell types both in vivo and in vitro. Since the ultimate objective of aneuploidy research is to obtain information that can be used to reduce the aneuploidy burden in humans, we have concentrated our research efforts on studying chemically-induced aneuploidy in mammalian germ cells and zygotes.

  8. Derivation of Trisomy 21 affected human embryonic stem cell line Genea053

    Directory of Open Access Journals (Sweden)

    Biljana Dumevska

    2016-03-01

    Full Text Available The Genea053 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Trisomy 21, indicative of Down Syndrome. Following ICM outgrowth on inactivated human feeders, CGH and STR analysis demonstrated a 47, XY, +21 karyotype and male allele pattern. The hESC line had pluripotent cell morphology and expressed pluripotent cell markers including 83% Nanog positive, 87% Oct4, 88% Tra1-60 and 98% SSEA4. The cell line was negative for Mycoplasma and visible contamination.

  9. Derivation of Trisomy 21 affected human embryonic stem cell line Genea053.

    Science.gov (United States)

    Dumevska, Biljana; McKernan, Robert; Goel, Divya; Schmidt, Uli

    2016-03-01

    The Genea053 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Trisomy 21, indicative of Down Syndrome. Following ICM outgrowth on inactivated human feeders, CGH and STR analysis demonstrated a 47, XY, +21 karyotype and male allele pattern. The hESC line had pluripotent cell morphology and expressed pluripotent cell markers including 83% Nanog positive, 87% Oct4, 88% Tra1-60 and 98% SSEA4. The cell line was negative for Mycoplasma and visible contamination. PMID:27346024

  10. Aneuploidy vs. gene mutation hypothesis of cancer: Recent study claims mutation but is found to support aneuploidy

    OpenAIRE

    Li, Ruhong; Sonik, Arvind; Stindl, Reinhard; Rasnick, David; Duesberg, Peter

    2000-01-01

    For nearly a century, cancer has been blamed on somatic mutation. But it is still unclear whether this mutation is aneuploidy, an abnormal balance of chromosomes, or gene mutation. Despite enormous efforts, the currently popular gene mutation hypothesis has failed to identify cancer-specific mutations with transforming function and cannot explain why cancer occurs only many months to decades after mutation by carcinogens and why solid cancers are aneuploid, although conventional mutation does...

  11. A Method to Quantify Cell-Free Fetal DNA Fraction in Maternal Plasma Using Next Generation Sequencing: Its Application in Non-Invasive Prenatal Chromosomal Aneuploidy Detection.

    Directory of Open Access Journals (Sweden)

    Xu-Ping Xu

    Full Text Available The fraction of circulating cell-free fetal (cff DNA in maternal plasma is a critical parameter for aneuploidy screening with non-invasive prenatal testing, especially for those samples located in equivocal zones. We developed an approach to quantify cff DNA fractions directly with sequencing data, and increased cff DNAs by optimizing library construction procedure.Artificial DNA mixture samples (360, with known cff DNA fractions, were used to develop a method to determine cff DNA fraction through calculating the proportion of Y chromosomal unique reads, with sequencing data generated by Ion Proton. To validate our method, we investigated cff DNA fractions of 2,063 pregnant women with fetuses who were diagnosed as high risk of fetal defects. The z-score was calculated to determine aneuploidies for chromosomes 21, 18 and 13. The relationships between z-score and parameters of pregnancies were also analyzed. To improve cff DNA fractions in our samples, two groups were established as follows: in group A, the large-size DNA fragments were removed, and in group B these were retained, during library construction.A method to determine cff DNA fractions was successfully developed using 360 artificial mixture samples in which cff DNA fractions were known. A strong positive correlation was found between z-score and fetal DNA fraction in the artificial mixture samples of trisomy 21, 18 and 13, as well as in clinical maternal plasma samples. There was a positive correlation between gestational age and the cff DNA fraction in the clinical samples, but no correlation for maternal age. Moreover, increased fetal DNA fractions were found in group A compared to group B.A relatively accurate method was developed to determine the cff DNA fraction in maternal plasma. By optimizing, we can improve cff DNA fractions in sequencing samples, which may contribute to improvements in detection rate and reliability.

  12. A Method to Quantify Cell-Free Fetal DNA Fraction in Maternal Plasma Using Next Generation Sequencing: Its Application in Non-Invasive Prenatal Chromosomal Aneuploidy Detection

    Science.gov (United States)

    Xu, Xu-Ping; Gan, Hai-Yan; Li, Fen-Xia; Tian, Qi; Zhang, Jun; Liang, Rong-Liang; Li, Ming

    2016-01-01

    Objective The fraction of circulating cell-free fetal (cff) DNA in maternal plasma is a critical parameter for aneuploidy screening with non-invasive prenatal testing, especially for those samples located in equivocal zones. We developed an approach to quantify cff DNA fractions directly with sequencing data, and increased cff DNAs by optimizing library construction procedure. Methods Artificial DNA mixture samples (360), with known cff DNA fractions, were used to develop a method to determine cff DNA fraction through calculating the proportion of Y chromosomal unique reads, with sequencing data generated by Ion Proton. To validate our method, we investigated cff DNA fractions of 2,063 pregnant women with fetuses who were diagnosed as high risk of fetal defects. The z-score was calculated to determine aneuploidies for chromosomes 21, 18 and 13. The relationships between z-score and parameters of pregnancies were also analyzed. To improve cff DNA fractions in our samples, two groups were established as follows: in group A, the large-size DNA fragments were removed, and in group B these were retained, during library construction. Results A method to determine cff DNA fractions was successfully developed using 360 artificial mixture samples in which cff DNA fractions were known. A strong positive correlation was found between z-score and fetal DNA fraction in the artificial mixture samples of trisomy 21, 18 and 13, as well as in clinical maternal plasma samples. There was a positive correlation between gestational age and the cff DNA fraction in the clinical samples, but no correlation for maternal age. Moreover, increased fetal DNA fractions were found in group A compared to group B. Conclusion A relatively accurate method was developed to determine the cff DNA fraction in maternal plasma. By optimizing, we can improve cff DNA fractions in sequencing samples, which may contribute to improvements in detection rate and reliability. PMID:26765738

  13. 多重探针连接依赖式扩增快速检测染色体非整倍体异常%Rapid detection of chromosomal aneuploidies by multiplex ligation-dependent probe amplification

    Institute of Scientific and Technical Information of China (English)

    范新萍; 王立荣; 肖白; 刘敬忠; 高淑英; 张璘; 张颖; 顾莹

    2008-01-01

    Objective To test whether multiplex ligation-dependent probe amplification(MLPA)could be used for the prenatal detection of the most common aneuploidies of chromosomes 13,18,21,X,and Y.Methods 34 cases including 22 blood samples(12 with trisomy 21,1 with monosomy X,one male witll extra Y and 8 healthy persons),4 cord blood samples with Down syndrome and 8 amniotic fluid samples ( 1 with trisomy 21 and 7 normal fetuses)were recruited into this study.All samples were confirmed by karvotype analysis. DNA was extracted from blood and amniotic lysate was incubated with proteinase K.MLPA was used to determine the relative copy numbers.Results The resuhs were available within 48 h and were concordant with karyotype analysis in all but one case of amniotic fluid that was suggested to be triploid sample 69,XXY by MLPA or contaminated by maternal blood.This sample actually was found containing a number of red blood cells after centfifugation in test. In total,the concordance rate with clinical characteristics was 97.1%.The Ratio values of 13,18,21,X in normal samples were approaching 1.0 except chromosome Y having slightly higher variation in relative copy number.The difference of ratio means between the normal and trisomy 21 samples was statistically significant by one-way ANOVA(F=298.906.P=0.000).Conclusion Computer assisted MLPA with high sensitivity is a rapid,simple,automatic and reliable method for detection of common chromosomal aneuploidies.%目的 评价多重探针连接依赖式扩增(muhiplex ligation-dependent probe amplification,MLPA)在常见染色体非整倍体异常及其在产前诊断中的应用价值.方法 收集经染色体核型分析证实的12例21三体、1例(45,X)、1例(47,XYY)患者,8名正常健康人外周血标本和4例21三体胎儿脐带血标本及1例21三体胎儿羊水、7例核型正常胎儿羊水,共计34份样本.提取外周血或脐带血基因组DNA,羊水标本蛋白酶K消化获得细胞裂解液,采用MLPA技术检测34

  14. 血清学筛查与胎儿超声检查在18、13三体综合征产前诊断中的临床应用%Clinical applications of serological screening and fetal ultrasonography for prenatal diagnosis of trisomy 18 and trisomy 13

    Institute of Scientific and Technical Information of China (English)

    梁学清; 韦丽萍; 唐娟

    2012-01-01

    Objective: To evaluate the values of serological screening and fetal ultrasonography in prenatal diagnosis of trisomy 18 and trisomy 13. Methods:A total of 780 pregnant women received serological screening and fetal ultrasonography, the samples of amnion fluid were obtained by amniocentesis, the cell culture and chromosomal karyotype analysis were conducted for prenatal diagnosis. Results; Among 780 fetuses, 6 fetuses were found with trisomy 18 and trisomy 13, the incidence was 0.77% , including 3 fetuses with trisomy 18 and 3 fetuses with trisomy 13. Three fetuses with trisomy 18 were found with high risk of serological screening and abnormal ultrasonic structure; and the other three fetuses were found with abnormal ultrasonic structure and low risk of serological screening. Conclusion: Serological screening of pregnant women combined with fetal ultrasonography is an effective method to detect trisomy 18 and trisomy 13 before delivery.%目的:评价利用孕妇血清学筛查与胎儿超声检查在18、13三体综合征胎儿产前诊断的价值.方法:对780例孕妇进行孕妇血清学筛查与胎儿超声检查,羊膜腔穿刺取羊水进行细胞培养染色体核型分析进行产前诊断.结果:780例胎儿中共发现6例18、13三体综合征,发生率为0.77%.其中3例18三体综合征,3例13三体综合征.3例18三体综合征血清学筛查高风险和超声结构异常,其余3例超声检查发现结构异常但血清学筛查为低风险.结论:孕妇血清筛查结合胎儿超声检查是产前检出18、13三体综合征胎儿的有效检查方法.

  15. Distal 5q trisomy resulting from an X;5 translocation detected by chromosome painting.

    Science.gov (United States)

    Abuelo, D N; Ahsanuddin, A N; Mark, H F

    2000-10-23

    We describe the case of a 13-year-old girl with an apparently de novo unbalanced translocation resulting in the presence of additional chromosomal material on the short arm of one X chromosome, which was detected by conventional G-banding studies. Fluorescence in situ hybridization (FISH) using the Chromoprobe Multiprobe-M protocol confirmed that the additional chromosomal material originated from chromosome 5. The karyotype of this patient is now established to be 46,X,der(X) t(X;5)(p22.3;q33), with a deletion of Xp22.3-pter and partial trisomy of 5q33-qter. The distal 5q trisomy genotype has been associated with clinical signs that include growth and mental retardation, eczema, craniofacial anomalies, and malformations of heart, lungs, abdomen, limbs, and genitalia. Our patient also has short stature, a prominent nasal bridge, a flat philtrum, a thin upper lip, dental caries, and limb and cardiac malformations, but she appears to be mildly affected compared with previously reported cases. This is the first case of distal 5q trisomy arising from a translocation with the X chromosome. Replication studies on this patient show that the derivative t(X;5) chromosome is late replicating in almost all cells examined, which indicates that this chromosome is preferentially inactivated. However, the translocated segment of chromosome 5 appears to be early replicating, which implies that the trisomic 5q segment is transcriptionally active. We cannot determine from these studies whether all or only some genes in this segment are expressed, but this patient's relatively mild clinical signs suggest that the critical region(s) that contribute to the distal 5q trisomy phenotype are at least partly suppressed. A review of other patients with X-chromosome translocations indicates that many but not all of them also have attenuated phenotypes. The mechanism of inactivation of autosomal material attached to the X chromosome is complex, with varying effects on the phenotype of the

  16. Non-invasive prenatal testing for aneuploidy and beyond: challenges of responsible innovation in prenatal screening.

    Science.gov (United States)

    Dondorp, Wybo; de Wert, Guido; Bombard, Yvonne; Bianchi, Diana W; Bergmann, Carsten; Borry, Pascal; Chitty, Lyn S; Fellmann, Florence; Forzano, Francesca; Hall, Alison; Henneman, Lidewij; Howard, Heidi C; Lucassen, Anneke; Ormond, Kelly; Peterlin, Borut; Radojkovic, Dragica; Rogowski, Wolf; Soller, Maria; Tibben, Aad; Tranebjærg, Lisbeth; van El, Carla G; Cornel, Martina C

    2015-11-01

    This paper contains a joint ESHG/ASHG position document with recommendations regarding responsible innovation in prenatal screening with non-invasive prenatal testing (NIPT). By virtue of its greater accuracy and safety with respect to prenatal screening for common autosomal aneuploidies, NIPT has the potential of helping the practice better achieve its aim of facilitating autonomous reproductive choices, provided that balanced pretest information and non-directive counseling are available as part of the screening offer. Depending on the health-care setting, different scenarios for NIPT-based screening for common autosomal aneuploidies are possible. The trade-offs involved in these scenarios should be assessed in light of the aim of screening, the balance of benefits and burdens for pregnant women and their partners and considerations of cost-effectiveness and justice. With improving screening technologies and decreasing costs of sequencing and analysis, it will become possible in the near future to significantly expand the scope of prenatal screening beyond common autosomal aneuploidies. Commercial providers have already begun expanding their tests to include sex-chromosomal abnormalities and microdeletions. However, multiple false positives may undermine the main achievement of NIPT in the context of prenatal screening: the significant reduction of the invasive testing rate. This document argues for a cautious expansion of the scope of prenatal screening to serious congenital and childhood disorders, only following sound validation studies and a comprehensive evaluation of all relevant aspects. A further core message of this document is that in countries where prenatal screening is offered as a public health programme, governments and public health authorities should adopt an active role to ensure the responsible innovation of prenatal screening on the basis of ethical principles. Crucial elements are the quality of the screening process as a whole (including non

  17. Double aortic arch with double aneuploidy-rare anomaly in combined Down and Klinefelter syndrome

    NARCIS (Netherlands)

    M.F. Gerretsen; W. Peelen; L.A.J. Rammeloo; D.R. Koolbergen; J. Hruda

    2009-01-01

    A 14-month-old boy with double aneuploidy and a double aortic arch suffered from frequently recurrent severe feeding and respiratory problems. Chromosomal analysis showed a 48,XXY + 21 karyotype: a double aneuploidy of Down syndrome (DS) and Klinefelter syndrome (KS). Only four cases of double aneup

  18. Cell‐free DNA testing in a trisomy 21 pregnancy with confined placental mosaicism for a cell line with trisomy for both chromosomes 18 and 21

    OpenAIRE

    Crooks, Kristy; Edwardsen, Ginger; O'Connor, Siobhan; Powell, Cynthia; Vargo, Diane; Vora, Neeta; Kaiser‐Rogers, Kathleen

    2015-01-01

    Key Clinical Message NIPT (noninvasive prenatal testing) detected trisomy for two chromosomes. One trisomy reflected the fetal karyotype, and the other resulted from CPM (confined placental mosaicism). This case illustrates that extensive cytogenetic analysis can be required to identify CPM, and that patients should be counseled regarding the possibility of discordant NIPT results.

  19. Clinical features and prognosis of a sample of patients with trisomy 13 (Patau syndrome) from Brazil.

    Science.gov (United States)

    Petry, Patrícia; Polli, Janaina B; Mattos, Vinícius F; Rosa, Rosana C M; Zen, Paulo R G; Graziadio, Carla; Paskulin, Giorgio A; Rosa, Rafael F M

    2013-06-01

    Trisomy 13 or Patau syndrome (PS) is a chromosomal disorder characterized by a well known presentation of multiple congenital anomalies. Our objective was to determine the clinical features and prognosis observed in a sample of patients with PS. The series was composed of patients with diagnosis of PS consecutively evaluated by a Clinical Genetics Service from a reference hospital of southern Brazil, in the period between 1975 and 2012. Statistical analysis was performed using PEPI program (version 4.0), with two-tailed Fisher's exact test for comparison of frequencies (P<0.05). The sample consisted of 30 patients, 60% male, median age at first evaluation of 9 days. Full trisomy of chromosome 13 was the main cytogenetic alteration (73%). The major clinical findings included: cryptorchidism (78%), abnormal auricles (77%), congenital heart defects (76%), polydactyly (63%), microphthalmia (60%) and micrognathia (50%). Four patients (13%) simultaneously had micro/anophthalmia, oral clefts and polydactyly. Some findings were only observed in our sample and included, among others, preauricular tags (10%), duplication of the hallux (3%) and spots following the lines of Blaschko (3%). Mosaicism (20% of cases) had a statistically significant association only with absence of cryptorchidism. The median of survival was 26 days. Patients with and without mosaicism had similar median of survival. Our findings, in agreement with the literature, show that the anomalies in patients with PS can be quite variable, sometimes even atypical. There is no pathognomonic finding, which may make the early identification of these patients challenging. PMID:23613355

  20. Prenatal Isolated Ventricular Septal Defect May Not Be Associated with Trisomy 21

    Directory of Open Access Journals (Sweden)

    Ori Shen

    2014-04-01

    Full Text Available The aim of this study was to examine if isolated fetal ventricular septal defect (VSD is associated with trisomy 21. One hundred twenty six cases with prenatal VSD diagnosed by a pediatric cardiologist were reviewed. Cases with known risk factors for congenital heart disease, the presence of other major anomalies, soft signs for trisomy 21 or a positive screen test for trisomy 21 were excluded. Ninety two cases formed the study group. None of the cases in the study group had trisomy 21. The upper limit of prevalence for trisomy 21 in isolated VSD is 3%. When prenatal VSD is not associated with other major anomalies, soft markers for trisomy 21 or a positive nuchal translucency or biochemical screen, a decision whether to perform genetic amniocentesis should be individualized. The currently unknown association between isolated VSD and microdeletions and microduplications should be considered when discussing this option.

  1. Trisomy 18 mosaicism in a 15-year-old boy with normal intelligence and short stature

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-05-08

    We report a 15-year-old boy with mosaicism for trisomy 18 and normal intelligence. Approximately 50% of his leukocytes are trisomic. This patient represents the sixth report of an individual with trisomy 18 mosaicism and normal intelligence. Those individuals with trisomy 18 mosaicism and normal intelligence need to be advised of increased risks for offspring with chromosome abnormalities and offered the option of prenatal diagnosis for cytogenetic anomalies. 6 refs.

  2. A live infant with trisomy 14 mosaicism and nuclear abnormalities of the neutrophils.

    Science.gov (United States)

    Dallapiccola, B; Ferranti, G; Giannotti, A; Novelli, G; Pasquini, L; Porfirio, B

    1984-01-01

    Mosaic trisomy 14 is described in a patient with severe developmental retardation and congenital malformations. Together with a few previous reports, this case suggests the existence of a syndrome associated with this chromosome imbalance. Hitherto unrecognised manifestations of trisomy 14 mosaicism were, in our patient, abnormalities of the neutrophil nuclei, which consisted of multiple pedunculated or sessile projections, similar to those characteristically associated with trisomy 13 syndrome. Images PMID:6512839

  3. A newborn with trisomy 13 who had tetralogy of Fallot and metopic synostosis: Case report

    OpenAIRE

    Karabel, M; Yolbaş, I; Kelekçi, S.; Şen, V; Haspolat, YK; Timuroğlu, L

    2013-01-01

    Background and Aim: Trisomy 13 (Patau syndrome) was first described by Patau et al in 1960. It is characterized by serious head, facial, and extremity anomalies, congenital heart defects, and mental abnormalities. The incidence rate of Trisomy 13 is 1/10.000 live births. Accompanying symptoms and findings vary in rate and severity among the cases. Tetralogy of Fallot and metopic synostosis are very rare abnormalities in patients with Trisomy 13. In this study, we aimed to present a newborn gi...

  4. Unilateral Ectrodactyly in a Newborn with Trisomy 18 Syndrome: An Unusual Association.

    Science.gov (United States)

    Kislal, Fatih Mehmet; Altuntas, Nilgun; Ozdemir, Osman; Ceylaner, Serdar; Kislal, Mustafa Hayri; Andiran, Nesibe

    2015-08-01

    The case of a newborn male with trisomy 18 syndrome, having bilateral syndactyly, aplasia and hypoplasia of the foot digits, unilateral ectrodactyly of the left foot and a prominently dorsiflexed hallux, clenched hand with overlapping fingers and general hypertonia, is presented. There are only 5 cases of trisomy 18 syndrome associated with ectrodactyly in the literature. We present a case of trisomy 18 syndrome with unilateral ectrodactyly of the left foot, which is an infrequent association. PMID:26305313

  5. Prenatal detection of Turner's syndrome in conjunction with trisomy 20 mosaicism (45,X/46, X, +0).

    OpenAIRE

    Watt, J L; Couzin, D A; Johnston, A.W.; Jandial, V; Gray, E. S.

    1981-01-01

    A case of Turner's syndrome, detected antenatally and complicated by the finding of trisomy 20 mosaicism in 50% of cells from each of two amniotic fluid cultures, is described. Cultures from seven fetal tissues in the subsequent abortus showed a predominance of 45,X cells, but nevertheless suggested the existence of a very low level of trisomy 20 mosaicism in three fetal tissues. The diagnostic dilemma in interpreting trisomy 20 mosaicism is discussed.

  6. Pattern of malformations in the axial skeleton in human trisomy 18 fetuses

    Energy Technology Data Exchange (ETDEWEB)

    Kjaer, I. [Univ. of Copenhagen (Denmark); Hansen, B.F. [Hvidovre Univ. Hospital (Denmark); Keeling, J.W. [Royal Hospital for Sick Children, Edinburgh (United Kingdom)

    1996-11-11

    We examined and described the development and abnormalities of the axial skeleton in 10 human trisomy 18 fetuses. Whole-body radiographs and radiographs of midsagittal tissue blocks of the cranial base and the spine were studied. In 3 fetuses no spinal radiographs were available. Seven osseous regions or fields along the body axis were analyzed, four in the spine, and three in the cranial base and nasal bones. Malformations occurred in the occipital field in all fetuses. This was a characteristic notching, either unilateral or bilateral, of the basilar part of the occipital bone. Nasal bones were abnormal in 8 cases, either absent or hypoplastic. Malformations were found in the thoracic and/or lumbosacral field in 7 fetuses. A single abnormality was found in the cervical spine in one fetus. The pattern of axial skeletal malformation in trisomy 18 fetuses recorded in the present study has not been described previously. Axial skeletal radiography should be included in autopsies of fetuses when chromosome disorders are present or suspected. The methods applied here are unaffected by autolysis. 26 refs., 5 figs.

  7. Application of quantitative fluorescence PCR for the prenatal diagnosis of common fetal chromosomal aneuploidies%定量荧光PCR在胎儿常见染色体非整倍体产前诊断中的应用

    Institute of Scientific and Technical Information of China (English)

    刘晓亮; 张媛媛; 崔婉婷; 何蓉; 赵彦艳

    2015-01-01

    目的 评估定量荧光PCR(quantitative fluorescent PCR,QF-PCR)技术在胎儿常见染色体非整倍体产前诊断中的应用.方法 收集孕18~22周羊水标本2436份,针对21、18、13、性染色体上共32个多态性短串联重复序列(short tandem repeat,STR)位点进行多重QF-PCR扩增及毛细管电泳,所有标本同时进行染色体核型分析.结果 QF-PCR检出胎儿染色体非整倍体76例(3.12%).其中21-三体51例,18-三体12例,13-三体2例,三倍体1例,上述结果与核型分析完全一致;QF-PCR提示性染色体数目异常10例,其中9例与核型分析结果一致,1例经核型分析证实为X染色体结构异常.此外,核型分析检出染色体结构异常24例(0.99%),仅1例QF-PCR显示部分STR位点异常,提示可能存在染色体结构异常;核型分析另检出染色体数目异常嵌合体2例(0.08%),仅1例QF-PCR显示临界值,提示可能为嵌合体.结论 QF-PCR可以准确的诊断21、18、13及性染色体的非整倍体改变,可以用于胎儿常见染色体非整倍体的产前快速筛查.%Objective To assess the value of quantitative fluorescence PCR (QF-PCR) for the prenatal diagnosis of common fetal chromosomal aneuploidies.Methods A total of 2436 amniotic fluid samples were collected at 18 to 22 gestational weeks.Multiplex QF-PCR was performed with fluorescencelabeled primers specific for 32 polymorphic short tandem repeat (STR) sites on chromosomes 21, 18, 13, X and Y.The PCR products were assayed by capillary electrophoresis.All samples were also assayed by karyotyping.Results Seventy-six (3.12%) samples were diagnosed as chromosomal aneuploidies by QF-PCR, among which 51 were trisomy 21, 12 were trisomy 18, 2 were trisomy 13, and 1 was triploidy.The results were all consistent with those of karyotyping.Ten samples were suspected as sex chromosomal aneuploidies, among which 9 were confirmed, except for 1 case with X structural abnormality.In addition,karyotyping has diagnosed 24 (0

  8. Neurophysiological findings in a newborn with chromosome 10 trisomy.

    Science.gov (United States)

    Vidale, Simone; Di Palma, Franco; Sironi, Luigi; Arnaboldi, Marco

    2014-01-01

    The trisomy of the short arm of chromosome 10 is a rare condition. The phenotypic expression of this genetic aberration is characterised by growth and mental retardation with several neurological signs. We report the neurophysiological findings in a newborn affected by 10p chromosome trisomy who developed seizures. Serial EEGs showed a progressive reduction in burst-suppression activity and a slow rhythmic basal activity. At 1 year of age the recording showed for the first time spikes of high amplitude (up to 800 μV) in bilateral frontal regions. These findings could be related to an asymmetrical cerebral maturation in the context of perinatal sufferance and brain malformation due to the genetic aberration.

  9. Incidence of X and Y Chromosomal Aneuploidy in a Large Child Bearing Population

    Science.gov (United States)

    Kırkızlar, Eser; Hall, Megan P.; Demko, Zachary; Zneimer, Susan M.; Curnow, Kirsten J.; Gross, Susan; Gropman, Andrea

    2016-01-01

    Background X&Y chromosomal aneuploidies are among the most common human whole-chromosomal copy number changes, but the population-based incidence and prevalence in the child-bearing population is unclear. Methods This retrospective analysis of prospectively collected data leveraged a routine non-invasive prenatal test (NIPT) using parental genotyping to estimate the population-based incidence of X&Y chromosome variations in this population referred for NIPT (generally due to advanced maternal age). Results From 141,916 women and 29,336 men, 119 X&Y chromosomal abnormalities (prevalence: 1 in 1,439) were identified. Maternal findings include: 43 cases of 45,X (40 mosaic); 30 cases of 47,XXX (12 mosaic); 3 cases of 46,XX uniparental disomy; 2 cases of 46,XY/46,XX; 23 cases of mosaicism of unknown type; 2 cases of 47,XX,i(X)(q10). Paternal findings include: 2 cases of 47,XXY (1 mosaic); 10 cases of 47,XYY (1 mosaic); 4 partial Y deletions. Conclusions Single chromosome aneuploidy was present in one of every 1,439 individuals considered in this study, showing 47,XXX; 47,XX,i(X)(q10); 47,XYY; 47,XXY, partial Y deletions, and a high level of mosaicism for 45,X. This expands significantly our understanding of X&Y chromosomal variations and fertility issues, and is critical for families and adults affected by these disorders. This current and extensive information on fertility will be beneficial for genetic counseling on prenatal diagnoses as well as for newly diagnosed postnatal cases. PMID:27512996

  10. Multifocal hepatoblastoma in a 6-month-old girl with trisomy 18: a case report

    Directory of Open Access Journals (Sweden)

    Kitanovski Lidija

    2009-06-01

    Full Text Available Abstract Introduction Edward's syndrome (trisomy 18 is a rare entity with a reported incidence of 1/3000 to 1/7000 births. Less than 10% of patients survive beyond the first year of life, which may influence the fact that malignant tumors are rarely reported in association with this syndrome. Case presentation The authors report a rare case of a 6-month-old girl with trisomy 18 and multifocal hepatoblastoma. The course of the disease, autopsy results and review of the literature are presented. Conclusion Our case represents the seventh published case of hepatoblastoma in a patient with trisomy 18. All of the seven published cases were women, possibly due to the high preponderance of females among the children with Edward's syndrome and longer survival of females with trisomy 18 compared to males. Since both trisomy 18 and hepatoblastoma are rare conditions, the probability that a child with trisomy 18 will independently develop a hepatoblastoma is very low. Therefore, we believe that the existence of these cases in children with trisomy 18 indicates a significant association. It can be assumed that trisomy 18 potentiates the development of hepatoblastoma. Careful clinical and post-mortem studies are needed to recognize the real frequency of hepatoblastoma in children with trisomy 18, who might die from different causes with unrecognizable hepatoblastoma.

  11. Prenatal Isolated Ventricular Septal Defect May Not Be Associated with Trisomy 21

    OpenAIRE

    Ori Shen; Sari Lieberman; Benjamin Farber; Daniel Terner; Amnon Lahad; Ephrat Levy-Lahad

    2014-01-01

    The aim of this study was to examine if isolated fetal ventricular septal defect (VSD) is associated with trisomy 21. One hundred twenty six cases with prenatal VSD diagnosed by a pediatric cardiologist were reviewed. Cases with known risk factors for congenital heart disease, the presence of other major anomalies, soft signs for trisomy 21 or a positive screen test for trisomy 21 were excluded. Ninety two cases formed the study group. None of the cases in the study group had trisomy 21. The ...

  12. Japanese neuropathy patients with peripheral myelin protein-22 gene aneuploidy

    Energy Technology Data Exchange (ETDEWEB)

    Lebo, R.V.; Li, L.Y.; Flandermeyer, R.R. [Univ. of California, San Francisco, CA (United States)] [and others

    1994-09-01

    Peripheral myelin protein (PMP-22) gene aneuploidy results in Charcot-Marie-Tooth disease Type 1A (CMT1A) and the Hereditary Neuropathy with Liability to Pressure Palsy (HNPP) in Japanese patients as well as Caucasian Americans. Charcot-Marie-Tooth disease (CMT), the most common genetic neuropathy, results when expression of one of at least seven genes is defective. CMT1A, about half of all CMT mutations, is usually associated with a duplication spanning the peripheral myelin protein-22 gene on distal chromosome band 17p11.2. Autosomal dominant HNPP (hereditary pressure and sensory neuropathy, HPSN) results from a deletion of the CMT1A gene region. Multicolor in situ hybridization with PMP-22 gene region probe characterized HNPP deletion reliably and detected all different size duplications reported previously. In summary, 72% of 28 Japanese CMT1 (HMSNI) patients tested had the CMT1A duplication, while none of the CMT2 (HMSNII) or CMT3 (HMSNIII) patients had a duplication. Three cases of HNPP were identified by deletion of the CMT1A gene region on chromosome 17p. HNPP and CMT1A have been reported to result simultaneously from the same unequal recombination event. The lower frequency of HNPP compared to CMT1A suggests that HNPP patients have a lower reproductive fitness than CMT1A patients. This result, along with a CMT1A duplication found in an Asian Indian family, demonstrates the broad geographic distribution and high frequency of PMP-22 gene aneuploidy.

  13. Constitutional partial 1q trisomy mosaicism and Wilms tumor.

    Science.gov (United States)

    Mark, Hon Fong L; Wyandt, Herman; Pan, Agen; Milunsky, Jeff M

    2005-10-15

    We report on a female patient with severe-profound mental retardation, multiple congenital anomalies, as well as a history of mosaicism for partial 1q trisomy in the amniotic fluid and a previous Wilms tumor specimen. Peripheral blood and fibroblasts were studied and did not demonstrate the mosaicism initially detected for 1q. Array comparative genomic hybridization yielded negative results. Additional cytogenetic studies helped clarify the previous findings and revealed evidence of partial 1q trisomy mosaicism in normal kidney tissue and in a kidney lesion. GTG-banded results showing low-percentage mosaicism for the structural rearrangement der(1)t(1;1)(p36.1;q23) in both tissues were corroborated by fluorescence in situ hybridization studies. We hypothesize that the partial 1q trisomy predisposed the target tissue (in this case kidney) to neoplasia. This study provides further support for the hypothesis that certain constitutional chromosomal abnormalities can predispose to cancer. As detection of a low-percentage mosaicism may be hampered by the limits imposed by currently available technology and the constraint of a finite sample size, extra vigilance in monitoring other somatic tissues will be needed throughout the patient's lifetime. Anticipatory clinical guidance and prognostication are meaningful only if given accurate cytogenetic diagnoses. To the best of our knowledge, this is the first reported case of Wilms tumor associated with constitutional partial 1q trisomy, either in pure or mosaic form, with the particular 1q23 breakpoint in conjunction with a break on 1p36.1. PMID:16213366

  14. Chromosomal Aneuploidies and Early Embryonic Developmental Arrest

    Directory of Open Access Journals (Sweden)

    Maria Maurer

    2015-07-01

    Full Text Available Background: Selecting the best embryo for transfer, with the highest chance of achieving a vital pregnancy, is a major goal in current in vitro fertilization (IVF technology. The high rate of embryonic developmental arrest during IVF treatment is one of the limitations in achieving this goal. Chromosomal abnormalities are possibly linked with chromosomal arrest and selection against abnormal fertilization products. The objective of this study was to evaluate the frequency and type of chromosomal abnormalities in preimplantation embryos with developmental arrest. Materials and Methods: This cohort study included blastomeres of embryos with early developmental arrest that were biopsied and analyzed by fluorescence in-situ hybridization (FISH with probes for chromosomes 13, 16, 18, 21 and 22. Forty-five couples undergoing IVF treatment were included, and 119 arrested embryos were biopsied. All probes were obtained from the Kinderwunsch Zentrum, Linz, Austria, between August 2009 and August 2011. Results: Of these embryos, 31.6% were normal for all chromosomes tested, and 68.4% were abnormal. Eleven embryos were uniformly aneuploid, 20 were polyploid, 3 were haploid, 11 displayed mosaicism and 22 embryos exhibited chaotic chromosomal complement. Conclusion: Nearly 70% of arrested embryos exhibit chromosomal errors, making chromosomal abnormalities a major cause of embryonic arrest and may be a further explanation for the high developmental failure rates during culture of the embryos in the IVF setting.

  15. Intracranial teratoma in children: the role of chromosome 21 trisomy.

    Science.gov (United States)

    Ferraz, Sabrine Teixeira; Valera, Elvis Terci; Brassesco, María Sol; Santos de Oliveira, Ricardo; Carlos dos Santos, Antonio; Saggioro, Fabiano Pinto; Neder, Luciano; Scrideli, Carlos Alberto; Tone, Luiz Gonzaga

    2014-04-01

    Teratomas are very rare intracranial tumors and cytogenetic information on this group remains rare. We report a case of a mature teratoma with abnormal +21 trisomy in tumor karyotype ocurring in a non-Down syndrome(DS) infant. Additionally, the evidence for the contribution of chromosome 21 trisomy in this neoplasia are briefly reviewed. The 6-month-old male baby presented with a posterior fossa tumor. Histological evaluation of tumor specimen showed a mature teratoma composed of fully differentiated ectodermal, mesodermal and endodermal components. Although somatic karyotyping of the index case was normal, composite tumor karyotype depicted 47,XY,+21[6]/46,XY[6]. Besides previous reports of children with DS and intracranial teratomas, this is the first report to describe the occurrence of an isolated chromosome 21 trisomy within the tumor of a non-DS child. The participation of chromosome 21 in this rare pediatric tumor, either somatic or restricted to tumor specimen,may deserve special interest and further investigation. PMID:24812702

  16. Partial trisomy 9p22 to 9p24.2 in combination with partial monosomy 9pter in a Syrian girl

    Directory of Open Access Journals (Sweden)

    Moassass Faten

    2010-10-01

    Full Text Available Abstract Background Partial trisomy of the short arm of chromosome 9 is among the most common autosomal structural chromosomal anomalies leading to chromosomal imbalance in human. Clinical characteristics are craniofacial dysmorphism including hypertelorism, prominent nose, deep-set eyes, and down-slanting palpebral fissures. The degree of clinical severity in partial trisomy 9p roughly correlates with the size of the chromosomal imbalance. Therefore, breakpoints as well as clinical findings need to be precisely defined for differential diagnosis. Results Chromosomes of a young female were analyzed due to primary amenorrhea, short stature, developmental delay and a characteristic facial appearance. Cytogenetic analysis using GTG banding identified a karyotype 46, XX, add(9pter. Surprisingly the application of high resolution molecular cytogenetic techniques characterized a partial trisomy 9p24.2-p22 and partial monosomy 9pter-p24.2. To the best of our knowledge only four similar case were reported by now. Conclusion Attempts for genotype-phenotype correlations for partial trisomy 9p might have been hampered by the fact that more complex, cryptic aberrations were neither considered nor detected in comparable clinical cases.

  17. Social Deficits in Male Children and Adolescents with Sex Chromosome Aneuploidy: A Comparison of XXY, XYY, and XXYY syndromes

    OpenAIRE

    Cordeiro, Lisa; Tartaglia, Nicole; Roeltgen, David; Ross, Judith

    2012-01-01

    We compare social skills in three groups of males with sex chromosome aneuploidies (SCAs) using the Social Responsiveness Scale (SRS). Participants included males with XXY (N=102, M=10.08 years), XYY (N=40, M=9.93 years), and XXYY (N=32, M=11.57 years). XXY had lower (better) SRS scores compared to XYY and XXYY. Scores were not significantly different between XYY and XXYY. In all groups, there were significantly more with SRS scores in the severe range compared to the SRS normative sample. Al...

  18. Fen1 mutations that specifically disrupt its interaction with PCNA cause aneuploidy-associated cancer

    Institute of Scientific and Technical Information of China (English)

    Li Zheng; Sankar Mitra; Qin Huang; Kemp H Kernstine; Gerd P Pfeifer; Binghui Shen; Huifang Dai; Muralidhar L Hegde; Mian Zhou; Zhigang Guo; Xiwei Wu; Jun WU; Lei Su; Xueyan Zhong

    2011-01-01

    DNA replication and repair are critical processes for all living organisms to ensure faithful duplication and transmission of genetic information. Flap endonuclease 1 (Feni), a structure-specific nuclease, plays an important role in multiple DNA metabolic pathways and maintenance of genome stability. Human FEN1 mutations that impair its exonuclease activity have been linked to cancer development. FEN1 interacts with multiple proteins, including proliferation cell nuclear antigen (PCNA), to form various functional complexes. Interactions with these proteins are considered to be the key molecular mechanisms mediating FEN1's key biological functions. The current challenge is to experimentally demonstrate the biological consequence of a specific interaction without compromising other functions of a desired protein. To address this issue, we established a mutant mouse model harboring a FEN1 point mutation (F343A/F344A, FFAA), which specifically abolishes the FEN1/PCNA interaction. We show that the FFAA mutation causes defects in RNA primer removal and long-patch base excision repair, even in the heterozygous state, resulting in numerous DNA breaks. These breaks activate the G2/M checkpoint protein, Chk1, and induce neartetraploid aneuploidy, commonly observed in human cancer, consequently elevating the transformation frequency. Consistent with this, inhibition of aneupioidy formation by a Chk1 inhibitor significantly suppressed the cellular transformation. WT/FFAA FEN1 mutant mice develop aneuploidy-associated cancer at a high frequency. Thus, this study establishes an exemplary case for investigating the biological significance of protein-protein interactions by knock-in of a point mutation rather than knock-out of a whole gene.

  19. Survival of children with trisomy 13 and trisomy 18: A multi-state population-based study.

    Science.gov (United States)

    Meyer, Robert E; Liu, Gang; Gilboa, Suzanne M; Ethen, Mary K; Aylsworth, Arthur S; Powell, Cynthia M; Flood, Timothy J; Mai, Cara T; Wang, Ying; Canfield, Mark A

    2016-04-01

    Trisomy 13 (T13) and trisomy 18 (T18) are among the most prevalent autosomal trisomies. Both are associated with a very high risk of mortality. Numerous instances, however, of long-term survival of children with T13 or T18 have prompted some clinicians to pursue aggressive treatment instead of the traditional approach of palliative care. The purpose of this study is to assess current mortality data for these conditions. This multi-state, population-based study examined data obtained from birth defect surveillance programs in nine states on live-born infants delivered during 1999-2007 with T13 or T18. Information on children's vital status and selected maternal and infant risk factors were obtained using matched birth and death certificates and other data sources. The Kaplan-Meier method and Cox proportional hazards models were used to estimate age-specific survival probabilities and predictors of survival up to age five. There were 693 children with T13 and 1,113 children with T18 identified from the participating states. Among children with T13, 5-year survival was 9.7%; among children with T18, it was 12.3%. For both trisomies, gestational age was the strongest predictor of mortality. Females and children of non-Hispanic black mothers had the lowest mortality. Omphalocele and congenital heart defects were associated with an increased risk of death for children with T18 but not T13. This study found survival among children with T13 and T18 to be somewhat higher than those previously reported in the literature, consistent with recent studies reporting improved survival following more aggressive medical intervention for these children. © 2015 Wiley Periodicals, Inc. PMID:26663415

  20. Trisomy 8 Acute Myeloid Leukemia Analysis Reveals New Insights of DNA Methylome with Identification of HHEX as Potential Diagnostic Marker

    OpenAIRE

    Saied, Marwa H.; Jacek Marzec; Sabah Khalid; Paul Smith; Gael Molloy; Young, Bryan D

    2015-01-01

    Trisomy 8 acute myeloid leukemia (AML) is the commonest numerical aberration in AML. Here we present a global analysis of trisomy 8 AML using methylated DNA immunoprecipitation-sequencing (MeDIP-seq). The study is based on three diagnostic trisomy 8 AML and their parallel relapse status in addition to nine non-trisomic AML and four normal bone marrows (NBMs). In contrast to non-trisomic DNA samples, trisomy 8 AML showed a characteristic DNA methylation distribution pattern because an increase...

  1. Prenatal diagnosis of craniomaxillofacial malformations: a characterization of phenotypes in trisomies 13, 18, and 21 by ultrasound and pathology.

    NARCIS (Netherlands)

    Ettema, A.M.; Wenghoefer, M.; Hansmann, M.; Carels, C.E.L.; Borstlap, W.A.; Berge, S.J.

    2010-01-01

    OBJECTIVE: To determine the relationship between trisomies 13, 18, and 21 and craniofacial malformations detected by prenatal sonography. DESIGN: During a 29-year period (1976 through 2004), prenatal sonographic findings of 69 fetuses with trisomy 13; 171 fetuses with trisomy 18; 302 fetuses with tr

  2. One carbon metabolism and trisomy 21 : analysis of the impact of genetic polymorphism

    NARCIS (Netherlands)

    Chango, A; Mircher, C; James, SJ; Rethore, MO; Nicolas, JP

    2002-01-01

    Trisomy 21 is the most common chromosome abnormality characterized by the presence of three copies of chromosome 21 in the genome. The clinical disorder attributed to trisomy 21 is Down syndrome. Patients with Down syndrome are heterogeneous in their phenotypic expression. Due to the location of the

  3. Characterization of partial trisomy 9p due to insertional translocation by chromosomal (micro)FISH

    NARCIS (Netherlands)

    de Pater, JM; Ippel, PF; van Dam, WM; Loneus, WH; Engelen, JJM

    2002-01-01

    We describe a family with an insertion 12;9 translocation occurring in a balanced form in a mother and two sons, but in an unbalanced form in the proband, resulting in trisomy of chromosome region 9p22-->9p24. The proband manifests typical features of trisomy 9p; the clinical signs were mental and g

  4. Rapid-prenatal diagnosis through fluorescence in situ hybridization for preventing aneuploidy related birth defects

    Directory of Open Access Journals (Sweden)

    Ashish Fauzdar

    2013-01-01

    Conclusion: Rapid FISH is a reliable and prompt method for detecting numerical chromosomal aberrations and has now been implemented as a routine diagnostic procedure for detection of fetal aneuploidy in India.

  5. Maternal plasma fetal DNA fractions in pregnancies with low and high risks for fetal chromosomal aneuploidies.

    Directory of Open Access Journals (Sweden)

    Irena Hudecova

    Full Text Available Recently published international guidelines recommend the clinical use of noninvasive prenatal test (NIPT for aneuploidy screening only among pregnant women whose fetuses are deemed at high risk. The applicability of NIPT to aneuploidy screening among average risk pregnancies requires additional supportive evidence. A key determinant of the reliability of aneuploidy NIPT is the fetal DNA fraction in maternal plasma. In this report, we investigated if differences in fetal DNA fractions existed between different pregnancy risk groups. One hundred and ninety-five singleton pregnancies with male fetuses divided into 3 groups according to first trimester screening parameters were examined for fetal DNA percentage by counting Y chromosome DNA sequences using massively parallel sequencing. Fetal DNA fractions were compared between risk groups and assessed for correlations with first trimester screening parameters. There was no statistically significant difference in fetal DNA fractions across the high, intermediate and low risk groups. Fetal DNA fraction showed a strong negative correlation with maternal weight. Fetal DNA fraction also showed weak but significant correlations with gestational age, crown-rump length, multiple of medians of free β-subunit of human chorionic gonadotropin and pregnancy-associated plasma protein A. Similar fetal DNA fractions in maternal plasma between high, intermediate and low risk pregnant women is a precondition for uniform performance of the aneuploidy NIPTs for the general population. This study thus shows that the aneuploidy screening by NIPT is likely to offer similar analytical reliability without respect to the a priori fetal aneuploidy risk.

  6. High modal number and triple trisomies are highly correlated favorable factors in childhood B-cell precursor high hyperdiploid acute lymphoblastic leukemia treated according to the NOPHO ALL 1992/2000 protocols

    DEFF Research Database (Denmark)

    Paulsson, Kajsa Maria; Forestier, Erik; Andersen, Mette K;

    2013-01-01

    Between 1992 and 2008, 713 high hyperdiploid acute lymphoblastic leukemias in children aged 1-15 years were diagnosed and treated according to the Nordic Society for Pediatric Hematology and Oncology acute lymphoblastic leukemia 1992/2000 protocols. Twenty (2.8%) harbored t(1;19), t(9;22), der(11q......23), or t(12;21). The median age of patients with "classic" high hyperdiploidy was lower than that of patients with translocation-positive high hyperdiploidy (P53/55 (P=0.020/0.024). In multivariate analyses, modal number and triple trisomies were significantly associated with superior event......-free survival in separate analyses with age and white blood cell counts. When including both modal numbers and triple trisomies, only low white blood cell counts were significantly associated with superior event-free survival (P=0.009). We conclude that high modal chromosome numbers and triple trisomies...

  7. Correlation of HER2 overexpression with gene amplification and its relation to chromosome 17 aneuploidy: a 5-year experience with invasive ductal and lobular carcinomas.

    Science.gov (United States)

    Nassar, Aziza; Khoor, Andras; Radhakrishnan, Reshmitha; Radhakrishnan, Anu; Cohen, Cynthia

    2014-01-01

    The HER2 oncogene shows expression or amplification, or both, in approximately 15% to 20% of breast cancers and has been associated with poor prognosis and a response to trastuzumab therapy. HER2 gene status determines the eligibility of breast cancer patients for trastuzumab therapy and a large fraction (41-56%) of these patients respond to targeted therapy. Several studies have related the increased expression of HER2 to an increased copy number of chromosome 17, rather than amplification of the HER2 gene. We compared the results of immunohistochemistry and fluorescence in situ hybridization in both invasive ductal and invasive lobular carcinomas, to determine the frequency of chromosome 17 aneuploidy associated with discordant results. In total, 390 invasive ductal carcinomas and 180 invasive lobular carcinomas diagnosed from January 2000 to December 2005 were included in the study only if results were available for immunohistochemistry (HercepTest; DAKO, Carpinteria, California) and fluorescence in situ hybridization (PathVysion HER2 DNA Probe Kit; Abbott Laboratories, Des Plaines, Illinois). Tumors classified as invasive ductal carcinomas were graded according to the Bloom-Richardson grading system. Correlation between the results of immunohistochemistry and fluorescence in situ hybridization was performed for all categories. Among invasive ductal carcinomas, 29% (115/390) showed chromosome 17 aneuploidy, mostly associated with grade 3/HER2 2+ (45%) or grade 2/HER2 3+ (55%) that were not amplified. Also, 34% (12/35) of invasive lobular carcinomas showed chromosome 17 aneuploidy; approximately one-third of these cases were HER2 2+ (33%) and HER2 3+ (37%) that were not amplified. Discordance between the results of immunohistochemistry and fluorescence in situ hybridization in both ductal and lobular carcinomas is largely associated with chromosome 17 aneuploidy.

  8. Parental exposure to environmental concentrations of diuron leads to aneuploidy in embryos of the Pacific oyster, as evidenced by fluorescent in situ hybridization

    International Nuclear Information System (INIS)

    Highlights: • FISH was realized on oyster embryos from diuron-exposed genitors. • rDNA genes were used as probes on the interphase nuclei of embryo preparations. • Higher aneuploidy level was observed in embryos from diuron-exposed genitors. • Hypo- and hyperdiploid (triploid) nuclei were detected. - Abstract: Changes in normal chromosome numbers (i.e. aneuploidy) due to abnormal chromosome segregation may arise either spontaneously or as a result of chemical/radiation exposure, particularly during cell division. Coastal ecosystems are continuously subjected to various contaminants originating from urban, industrial and agricultural activities. Genotoxicity is common to several families of major environmental pollutants, including pesticides, which therefore represent a potential important environmental hazard for marine organisms. A previous study demonstrated the vertical transmission of DNA damage by subjecting oyster genitors to short-term exposure to the herbicide diuron at environmental concentrations during gametogenesis. In this paper, Fluorescent in situ hybridization (FISH) was used to further characterize diuron-induced DNA damage at the chromosomal level. rDNA genes (5S and 18-5.8-28S), previously mapped onto Crassostrea gigas chromosomes 4, 5 and 10, were used as probes on the interphase nuclei of embryo preparations. Our results conclusively show higher aneuploidy (hypo- or hyperdiploidy) level in embryos from diuron-exposed genitors, with damage to the three studied chromosomal regions. This study suggests that sexually developing oysters are vulnerable to diuron exposure, incurring a negative impact on reproductive success and oyster recruitment

  9. Parental exposure to environmental concentrations of diuron leads to aneuploidy in embryos of the Pacific oyster, as evidenced by fluorescent in situ hybridization

    Energy Technology Data Exchange (ETDEWEB)

    Barranger, Audrey, E-mail: audrey.barranger@ifremer.fr [Ifremer, SG2M, Laboratory of Genetics and Pathology of Marine Molluscs, Avenue de Mus du Loup, 17390 La Tremblade (France); Ifremer, Department of Biogeochemistry and Ecotoxicology, Laboratory of Ecotoxicology, Rue de l’Ile d’Yeu, BP 21105, 44311 Nantes Cedex 03 (France); Benabdelmouna, Abdellah, E-mail: abdellah.benabdelmouna@ifremer.fr [Ifremer, SG2M, Laboratory of Genetics and Pathology of Marine Molluscs, Avenue de Mus du Loup, 17390 La Tremblade (France); Dégremont, Lionel [Ifremer, SG2M, Laboratory of Genetics and Pathology of Marine Molluscs, Avenue de Mus du Loup, 17390 La Tremblade (France); Burgeot, Thierry; Akcha, Farida [Ifremer, Department of Biogeochemistry and Ecotoxicology, Laboratory of Ecotoxicology, Rue de l’Ile d’Yeu, BP 21105, 44311 Nantes Cedex 03 (France)

    2015-02-15

    Highlights: • FISH was realized on oyster embryos from diuron-exposed genitors. • rDNA genes were used as probes on the interphase nuclei of embryo preparations. • Higher aneuploidy level was observed in embryos from diuron-exposed genitors. • Hypo- and hyperdiploid (triploid) nuclei were detected. - Abstract: Changes in normal chromosome numbers (i.e. aneuploidy) due to abnormal chromosome segregation may arise either spontaneously or as a result of chemical/radiation exposure, particularly during cell division. Coastal ecosystems are continuously subjected to various contaminants originating from urban, industrial and agricultural activities. Genotoxicity is common to several families of major environmental pollutants, including pesticides, which therefore represent a potential important environmental hazard for marine organisms. A previous study demonstrated the vertical transmission of DNA damage by subjecting oyster genitors to short-term exposure to the herbicide diuron at environmental concentrations during gametogenesis. In this paper, Fluorescent in situ hybridization (FISH) was used to further characterize diuron-induced DNA damage at the chromosomal level. rDNA genes (5S and 18-5.8-28S), previously mapped onto Crassostrea gigas chromosomes 4, 5 and 10, were used as probes on the interphase nuclei of embryo preparations. Our results conclusively show higher aneuploidy (hypo- or hyperdiploidy) level in embryos from diuron-exposed genitors, with damage to the three studied chromosomal regions. This study suggests that sexually developing oysters are vulnerable to diuron exposure, incurring a negative impact on reproductive success and oyster recruitment.

  10. Report of a Case with Trisomy 9 Mosaicism

    Directory of Open Access Journals (Sweden)

    Mohammad Miryounesi

    2016-05-01

    Full Text Available Trisomy 9 is a rare chromosome disorder with high neonatal mortality. It is often seen in mosaic form. Most patients who survive are severely mentally retarded. The main features of this syndrome are “bulbous” nose, microphthalmia, dislocated limbs, and other anomalies of skeletal, cardiac, genitourinary, and central nervous system. Most patients have developmental and cognitive impairment. Patients with mosaicism survive longer than non-mosaics, but it was believed that the degree of mosaicism in lymphocytes or fibroblasts does not associate with survival or degree of impairment. In this report, we present a 2.5-year-old male case of mosaic trisomy 9, to show the wide range of clinical findings in this chromosome disorder. The patient had cardiac anomalies, inguinal hernia, and undescendent testes. He had low-set slightly malformed ears, deeply-set malformed eyes, small palpebral fissures, micrognathia, developmental delay and unilateral optic hypoplasia. The most prominent facial anomaly in this patient was eye anomalies. Cytogenetic analysis with G banding showed karyotype 47XY,+9 in 44% of peripheral lymphocytes examined (47XY,+9[22], 46XY[28]. His parents’ karyotypes were normal. Moderate developmental delay, which was detected in this patient shows that the range of motor and cognitive impairment in this chromosomal disorder is quite broad. This fact should be considered in genetic counseling as well as prenatal diagnosis of this chromosomal disorder.

  11. Delineation of a characteristic phenotype in distal trisomy 2q.

    Science.gov (United States)

    Kyllerman, M; Wahlström, J; Westerberg, B; Gustavson, K H

    1984-12-01

    A recombinant chromosome change with dup(2)(q34----qter) secondary to a paternal inv(2) (pter----q34) was found in a 19-year-old boy and his 12-year-old sister. Both were born at term with normal birth weight and head circumference. Hypertelorism, irregular nystagmus, broad flat nasal bridge, and short beaked nose with anteverted nostrils were noted neonatally. Both developed microcephaly and brachycephaly. Cardiac, urogenital, retinal, and optic disc anomalies and onset of progressive kyphosis in adolescence were detected. Their facial appearance, with birdlike "Muppet Gonzo" features, was increasingly accentuated with age. Both had mild mental retardation with IQ's around 70. The clinical findings in these siblings were compared with those described in 23 cases with various 2q partial trisomies. The results of the present study and previous studies indicate a characteristic clinical presentation in children and adults. The reluctance to define the specific phenotype for distal 2q trisomy might be due to the fact that the clinical features tend to be considerably more pronounced towards adolescence than neonatally. PMID:6543860

  12. A girl with metopic synostosis and trisomy 13 mosaicism: case report and review of the literature.

    Science.gov (United States)

    Aypar, Ebru; Yildirim, M Selman; Sert, Ahmet; Ciftci, Ilhan; Odabas, Dursun

    2011-03-01

    Trisomy 13, or Patau syndrome is a rare chromosomal disorder characterized by a triad of cleft lip and palate, postaxial polydactyly and microcephaly. Complete, partial, or mosaic forms of the disorder can occur. Mosaic trisomy 13 is very rare, it occurs in only 5% of all patients with trisomy 13 phenotype. Metopic synostosis (MS) is premature fusion of the metopic suture, which is part of the frontal suture. It results in a V-shaped abnormality at the front of the skull. MS may occur in a syndromic or nonsyndromic form. We report on a 24-day-old girl with hypotonia, MS, trigonocephaly, capillary hemangioma, hypotelorism, upward slanting palpebral fissures, epicanthal folds, small nose with anteverted nares, high palate, ankyloglossia, long philtrum, low-set ears, short neck, postaxial polydactyly of both hands and feet and congenital heart defect. Cytogenetic analysis demonstrated trisomy 13 mosaicism; 46,XX[58]/47,XX,+13[42]. Although MS has been previously reported in complete and partial forms of trisomy 13, it has not been reported in mosaic form of trisomy 13. Our report supports the evidence that trisomy 13 causes MS. It also emphasizes the need for cytogenetic investigations in patients presenting with MS and multiple congenital anomalies for providing accurate diagnosis, genetic counseling, and prenatal diagnosis. PMID:21344634

  13. Partial trisomy 14q and monosomy 20q due to an unbalanced familial translocation

    Energy Technology Data Exchange (ETDEWEB)

    Menasse-Palmer, L; Leo, J.; Cannizaro, L. [Albert Einstein College of Medicine, Bronx, NY (United States)] [and others

    1994-09-01

    Partial trisomy of distal 14q and monosomy of 20q are rare. There have been several reports of a partial distal trisomy 14q with characteristic clinical findings, including hypogonadism and a conotruncal cardiac anomaly. There is no deletion distal 20q syndrome. We have recently examined a newborn with this unique duplication/deletion syndrome. Case report: J.S. was the 2980 gm product of a term uneventful pregnancy delivered to a 24-year-old gravida 2, para 1001 mother. The newborn exam revealed a dysmorphic newborn male with a sloping forehead, bitemporal narrowing, glabellar furrowing and micrognathia. A systolic murmur was audible. The genital abnormalities were micropenis, hypospadias with chordee and bifid scrotum with prominent raphe, and gonads were palpable. A CAT scan of the head revealed grade I IVH. An echocardiogram showed a VSD, ASD and an AP window. A sonogram of the liver showed absence of the gallbladder. Chromosome analysis revealed an abnormal male karyotype containing a derivative 20, subsequently shown to be inherited as a result of malsegregation of a paternal translocation: 46,XY,-20,+der(20)t(14;20)(q32.1;q13.3)pat. The infant fed poorly and required tube feedings and was treated for congestive heart failure with Digoxin, Lasix and oxygen. A decreased cortisol level and cholestasis were noted. The infant died after a cardiopulmonary arrest at one month of age. No post-mortem was obtained. Clinical cytogenetic correlation (conotruncal abnormality and hypogonadism) with partial duplication of distal 14q was positive. This case helps to further delineate duplication 14q and a syndrome due to partial deletion 20q.

  14. Acute Myeloid Leukemia with Isolated Trisomy 19 Associated with Diffuse Myelofibrosis and Osteosclerosis

    Directory of Open Access Journals (Sweden)

    Adam Stelling

    2015-12-01

    Full Text Available Primary myelofibrosis (PMF, per WHO criteria, is a clonal myeloproliferative neoplasm that usually presents with a proliferation of granulocytic and megakaryocytic lineages with an associated fibrous deposition and extramedullary hematopoiesis. The bone marrow histologic findings of this disorder are typically characterized by the presence of myeloid metaplasia with an associated reactive fibrosis, angiogenesis, and osteosclerosis. However, marked myelofibrosis is not solely confined to PMF and may also be associated with other conditions including but not limited to acute megakaryoblastic leukemias (FAB AML-M7. Here, we describe a rare case of a non-megakaryoblastic acute myeloid leukemia with marked myelofibrosis with osteosclerosis and an isolated trisomy 19. A 19-year-old male presented with severe bone pain of one week duration with a complete blood cell count and peripheral smear showing a mild anemia and occasional circulating blasts. A follow up computed tomography (CT scan showed diffuse osteosclerosis with no evidence of hepatosplenomegaly or lymphadenopathy. Subsequently, the bone marrow biopsy showed markedly sclerotic bony trabeculae and a hypercellular marrow with marked fibrosis and intervening sheets of immature myeloid cells consistent with myeloblasts with monocytic differentiation. Importantly, these myeloblasts were negative for megakaryocytic markers (CD61 and vWF, erythroid markers (hemoglobin and E-cadherin, and lymphoid markers (CD3, CD19, and TdT. Metaphase cytogenetics showed an isolated triosomy 19 with no JAK2 V617F mutation. The patient was treated with induction chemotherapy followed by allogenic hematopoietic stem cell transplantation which subsequently resulted in a rapid resolution of bone marrow fibrosis, suggesting graft-anti-fibrosis effect. This is a rare case of a non-megakaryoblastic acute myeloid leukemia with myelofibrosis and osteosclerosis with trisomy 19 that may provide insights into the prognosis and

  15. Trisomy 8, a Cytogenetic Abnormality in Myelodysplastic Syndromes, Is Constitutional or Not?

    OpenAIRE

    Sílvia Saumell; Francesc Solé; Leonor Arenillas; Julia Montoro; David Valcárcel; Carme Pedro; Carmen Sanzo; Elisa Luño; Teresa Giménez; Montserrat Arnan; Helena Pomares; Raquel De Paz; Beatriz Arrizabalaga; Andrés Jerez; Martínez, Ana B.

    2015-01-01

    Isolated trisomy 8 is not considered presumptive evidence of myelodysplastic syndrome (MDS) in cases without minimal morphological criteria. One reason given is that trisomy 8 (+8) can be found as a constitutional mosaicism (cT8M). We tried to clarify the incidence of cT8M in myeloid neoplasms, specifically in MDS, and the diagnostic value of isolated +8 in MDS. Twenty-two MDS and 10 other myeloid neoplasms carrying +8 were studied. Trisomy 8 was determined in peripheral blood by conventional...

  16. Trisomy 19 and T(9;22 In a Patient with Acute Basophilic Leukemia

    Directory of Open Access Journals (Sweden)

    Alicia Rojas-Atencio

    2011-01-01

    Full Text Available We report a case of acute basophilic leukemia with two coexisting clonal abnormalities, t(9;22 and trisomy 19. The blast showed positive reaction with myeloperoxidase but negative reaction with chloroacetate esterase and acid phosphatase. Metachromatic features of the blast were observed with toluidine blue stain. Ultrastructure study showed the presence of azurophilic granules in basophils and blast mast cells. Conventional and molecular cytogenetic studies revealed, t(9;22 with BCR/ABL positive and trisomy 19 in all metaphase cells. To our knowledge, this paper here is the first to present acute basophilic leukemia with trisomy 19 and t(9;22.

  17. A patient with trisomy 13 mosaicism with an unusual skin pigmentary pattern and prolonged survival.

    Science.gov (United States)

    González-del Angel, Ariadna; Estandia-Ortega, Bernardette; Gaviño-Vergara, Alejandro; Sáez-de-Ocariz, Marimar; Velasco-Hernández, María de la Luz; Salas-Labadía, Consuelo

    2014-01-01

    Trisomy 13, or Patau syndrome, is a chromosomal disorder that can occur in complete, partial, or mosaic forms. Mosaicism is observed in 6% of individuals with trisomy 13 and, in contrast to the complete form, has wide phenotypic variability, longer survival, and in some patients an unusual skin pigmentary pattern similar to phylloid hypomelanosis. We describe here a 12-year-old girl with trisomy 13 mosaicism (mos 47,XX,+13[9]/46,XX[16]) who had three major malformations, an unusual skin pigmentary pattern, and prolonged survival. PMID:24846410

  18. Application of fluorescence in situ hybridization in rapid prenatal diagnosis of chromosome aneuploidy in uncultured amniotic fluid samples%FISH技术在产前诊断胎儿染色体数异常中的应用

    Institute of Scientific and Technical Information of China (English)

    张利平; 剡红民; 秦翠云; 娄超; 马晓萍; 郑军; 强荣

    2011-01-01

    目的 探讨荧光原位杂交(FISH)技术在快速产前诊断胎儿染色体非整倍体异常中的价值.方法 使用荧光原位杂交技术,选用荧光素标记的双色13/21染色体位点特异性探针和三色18/X/Y染色体着丝粒探针,检测760例胎儿羊水细胞.结果 采用双色13/21号和三色18/X/Y染色体荧光探针检测间期未培养羊水细胞,发现8例21三体综合征,1例13三体综合征,1例45,XO,1例47,XXX,3例性染色体嵌合体.荧光原位杂交检测结果 和常规细胞遗传学检测结果 相比,两者符合率为99%.结论 荧光原位杂交技术在产前快速诊断胎儿染色体非整倍体异常有很高的临床价值.%Objective To investgate clinical value of fluorescence in situ hybridization (FISH) in rapid prenatal diagnosis of chromosome aneuploidy of the fetus. Methods Fluorescein-labeled bicolor 13th/21th chromosomal loci specificity probe and triad colour 18th/X/Y kinomere probe were used to detect cells in uncultured amniotic fluid samples of 760 pregnact women. Results 8 fetuses with trisomy 21 syndrome, I fetus with trisomy 13 syndrome, I fetus with with 45 ,XO, 1 fetus with 47,XXX and 5 fetuses with sex chromosome mosaic syndrome were identified. The coincidence rate of diagnosis between FISH and conventional cytogenetics was 99%. Conclusion FISH technique has a high clinic value in rapid diagnosis of chromosome aneuploidy.

  19. Sex chromosome aneuploidy in cytogenetic findings of referral patients from south of Iran

    Directory of Open Access Journals (Sweden)

    Najmeh Jouyan

    2012-01-01

    Full Text Available Background: Chromosome abnormality (CA including Sex chromosomes abnormality (SCAs is one of the most important causes of disordered sexual development and infertility. SCAs formed by numerical or structural alteration in X and Y chromosomes, are the most frequently CA encountered at both prenatal diagnosis and at birth. Objective: This study describes cytogenetic findings of cases suspected with CA referred for cytogenetic study. Materials and Methods: Blood samples of 4151 patients referred for cytogenetic analysis were cultured for chromosome preparation. Karyotypes were prepared for all samples and G-Banded chromosomes were analyzed using x100 objective lens. Sex chromosome aneuploidy cases were analyzed and categorized in two groups of Turners and Klinefelter’s syndrome (KFS. Results: Out of 230 (5.54% cases with chromosomally abnormal karyotype, 122 (30% cases suspected of sexual disorder showed SCA including 46% Turner’s syndrome, 46% KFS and the remaining other sex chromosome abnormalities. The frequency of classic and mosaic form of Turner’s syndrome was 33% and 67%, this was 55% and 45% for KFS, respectively. Conclusion: This study shows a relatively high sex chromosome abnormality in this region and provides cytogenetic data to assist clinicians and genetic counselors to determine the priority of requesting cytogenetic study. Differences between results from various reports can be due to different genetic background or ethnicity.

  20. Allelic variation, aneuploidy, and nongenetic mechanisms suppress a monogenic trait in yeast.

    Science.gov (United States)

    Sirr, Amy; Cromie, Gareth A; Jeffery, Eric W; Gilbert, Teresa L; Ludlow, Catherine L; Scott, Adrian C; Dudley, Aimée M

    2015-01-01

    Clinically relevant features of monogenic diseases, including severity of symptoms and age of onset, can vary widely in response to environmental differences as well as to the presence of genetic modifiers affecting the trait's penetrance and expressivity. While a better understanding of modifier loci could lead to treatments for Mendelian diseases, the rarity of individuals harboring both a disease-causing allele and a modifying genotype hinders their study in human populations. We examined the genetic architecture of monogenic trait modifiers using a well-characterized yeast model of the human Mendelian disease classic galactosemia. Yeast strains with loss-of-function mutations in the yeast ortholog (GAL7) of the human disease gene (GALT) fail to grow in the presence of even small amounts of galactose due to accumulation of the same toxic intermediates that poison human cells. To isolate and individually genotype large numbers of the very rare (∼0.1%) galactose-tolerant recombinant progeny from a cross between two gal7Δ parents, we developed a new method, called "FACS-QTL." FACS-QTL improves upon the currently used approaches of bulk segregant analysis and extreme QTL mapping by requiring less genome engineering and strain manipulation as well as maintaining individual genotype information. Our results identified multiple distinct solutions by which the monogenic trait could be suppressed, including genetic and nongenetic mechanisms as well as frequent aneuploidy. Taken together, our results imply that the modifiers of monogenic traits are likely to be genetically complex and heterogeneous. PMID:25398792

  1. Aneuploidy involving chromosome 1 may be an early predictive marker of intestinal type gastric cancer

    Energy Technology Data Exchange (ETDEWEB)

    Williams, L. [Royal Glamorgan Hospital, Ynysmaerdy, Llantrisant CF72 8XR (United Kingdom); Somasekar, A. [Institute of Life Science, Swansea School of Medicine, Swansea University, Swansea SA28PP (United Kingdom); Neath Port Talbot Hospital, Abertawe Bro Morgannwg University NHS Trust, Baglan Way, Port Talbot SA12 7BX (United Kingdom); Davies, D.J.; Cronin, J.; Doak, S.H. [Institute of Life Science, Swansea School of Medicine, Swansea University, Swansea SA28PP (United Kingdom); Alcolado, R. [Royal Glamorgan Hospital, Ynysmaerdy, Llantrisant CF72 8XR (United Kingdom); Williams, J.G. [Neath Port Talbot Hospital, Abertawe Bro Morgannwg University NHS Trust, Baglan Way, Port Talbot SA12 7BX (United Kingdom); Griffiths, A.P. [Department of Histopathology, Morriston Hospital, Abertawe Bro Morgannwg University NHS Trust, Morriston, SA66NL (United Kingdom); Baxter, J.N. [Department of Surgery, Morriston Hospital, Abertawe Bro Morgannwg University NHS Trust, Morriston, SA66NL (United Kingdom); Jenkins, G.J.S., E-mail: g.j.jenkins@swansea.ac.uk [Institute of Life Science, Swansea School of Medicine, Swansea University, Swansea SA28PP (United Kingdom)

    2009-10-02

    Intestinal type gastric cancer is a significant cause of mortality, therefore a better understanding of its molecular basis is required. We assessed if either aneuploidy or activity of the oncogenic transcription factor nuclear factor kappa B (NF-{kappa}B), increased incrementally during pre-malignant gastric histological progression and also if they correlated with each other in patient samples, as they are both induced by oxygen free radicals. In a prospective study of 54 (aneuploidy) and 59 (NF-{kappa}B) consecutive patients, aneuploidy was assessed by interphase fluorescent in situ hybridisation (FISH) for chromosome 1. NF-{kappa}B was assessed by expression of interleukin-8 (IL-8), and in a subset, by immunohistochemistry (IHC) for active p65. Aneuploidy levels increased incrementally across the histological series. 2.76% of cells with normal histology (95% CI, 2.14-3.38%) showed background levels of aneuploidy, this increased to averages of 3.78% (95% CI, 3.21-4.35%), 5.89% (95% CI, 3.72-8.06%) and 7.29% (95% CI, 4.73-9.85%) of cells from patients with gastritis, Helicobacter pylori positive gastritis and atrophy/intestinal metaplasia (IM) respectively. IL-8 expression was only increased in patients with current H. pylori infection. NF-{kappa}B analysis showed some increased p65 activity in inflamed tissues. IL-8 expression and aneuploidy level were not linked in individual patients. Aneuploidy levels increased incrementally during histological progression; were significantly elevated at very early stages of neoplastic progression and could well be linked to cancer development and used to assess cancer risk. Reactive oxygen species (ROS) induced in early gastric cancer are presumably responsible for the stepwise accumulation of this particular mutation, i.e. aneuploidy. Hence, aneuploidy measured by fluorescent in situ hybridisation (FISH) coupled to brush cytology, would be worthy of consideration as a predictive marker in gastric cancer and could be

  2. Detection of sex chromosome aneuploidy in dog spermatozoa by triple color fluorescence in situ hybridization.

    Science.gov (United States)

    Komaki, Haruna; Oi, Maya; Suzuki, Hiroshi

    2014-09-01

    With the development of a direct visualization of sex chromosome in a single sperm by fluorescence in situ hybridization (FISH) technique, the frequency of aberration (aneuploidy) in spermatozoa in several mammals has been investigated. However, there is no report in the incidence of X-Y aneuploidy in the sperm population of dogs. Therefore, in this study, the aneuploidy in dog spermatozoa was examined by multicolor FISH using specific molecular probes for canine sex chromosomes and autosome. Semen from eight male Labrador retrievers was used as specimen. For decondensation of sperm nuclei, the specimen was treated with 1 M NaOH for 4 minutes at room temperature. Probes for chromosomes X, Y, and 1, labeled with SpectrumGreen, Cy3 and Cy5, respectively, were hybridized with decondensed spermatozoa. Fluorescence in situ hybridization signals in sperm heads were clearly detected in each specimen, regardless of the sperm donor. The FISH signal of at least one of the three probes was detected in all sperm heads examined. There was no significant difference between the theoretical ratio (50:50) and the observed ratio of X and Y chromosomes in spermatozoa of all the eight dogs. Mean percentage of sex chromosome aneuploidy was 0.127% (ranged between 0% and 0.316%). This percentage of canine sex chromosome aneuploidy was lower than the one reported in cattle, horses, river buffalo, and goats sperm, but higher than that observed in mice and sheep.

  3. Detection of chromosomal aneuploidy in human preimplantation embryos by next-generation sequencing.

    Science.gov (United States)

    Wang, Li; Wang, Xiaohong; Zhang, Jianguang; Song, Zhuo; Wang, Shufang; Gao, Yang; Wang, Jun; Luo, Yaning; Niu, Ziru; Yue, Xiaojing; Xu, Genming; Cram, David S; Yao, Yuanqing

    2014-05-01

    Embryos produced by assisted reproductive technologies are commonly associated with a high level of aneuploidy. Currently, 24-chromosome profiling of embryo biopsy samples by array-based methods is available to identify euploid embryos for transfer that have a higher potential for implantation and development to term. From a laboratory and patient perspective, there is a need to explore the feasibility of developing an alternative method for routine aneuploidy assessment of embryos that would be more comprehensive, cost-effective, and efficient. We speculated that aneuploidy could be readily assessed in test single-cell biopsy samples by first performing whole genome amplification followed by library generation, massively parallel shot-gun sequencing, and finally bioinformatics analysis to quantitatively compare the ratio of uniquely mapped reads to reference cells. Using Down syndrome as an example, the copy number change for chromosome 21 was consistently 1.5-fold higher in multiple cell and single-cell samples with a 47,XX,+21 karyotype. Applying the validated sequencing strategy to 10 sister blastomeres from a single human embryo, we showed that the aneuploidy status called by sequencing was consistent with short tandem repeat allelic profiling. These validation studies indicate that aneuploidy detection using sequencing-based methodology is feasible for further improving the practice of preimplantation genetic diagnosis. PMID:24648399

  4. Corneal opacities--a diagnostic feature of the trisomy 8 mosaic syndrome.

    OpenAIRE

    Frangoulis, M; Taylor, D.

    1983-01-01

    An infant with trisomy 8 mosaicism had bilateral corneal opacities and multiple systemic anomalies. A review of the literature suggests that corneal opacities are a prominent feature of the syndrome and may have substantial clinical and diagnostic importance.

  5. Transient leukemia with trisomy 21: Description of a case and review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Bhatt, S.; Schreck, R.; Graham, J.M. [UCLA School of Medicine, Los Angeles, CA (United States)] [and others

    1995-09-25

    Transient myeloproliferative disease (TMD) is often associated with a trisomy 21 cell line, but it is not always associated with clinical signs of Down syndrome. We report on a phenotypically normal newborn boy who presented with a high white blood cell count, undifferentiated blasts, and cutaneous leukemic infiltrates and compare this patient with the literature on TMD and trisomy 21. Chromosome analysis of bone marrow, and subsequently of skin fibroblasts, documented constitutional mosaicism for trisomy 21. A decrease in the frequency of blast cells paralleled a decrease in cells demonstrating trisomy 21 in hematopoietic tissues, and a complete clinical recovery was seen without the use of chemotherapy. Recognition of this transient form of congenital leukemia is important to prevent the unnecessary use of toxic chemotherapeutic agents in such patients. 23 refs., 2 figs., 2 tabs.

  6. Trisomy 8 with a jumping addition in ANLL

    Energy Technology Data Exchange (ETDEWEB)

    Berger, C.S.; Bull, R.M.; Barr, L. [Oncogenetics, Phoenix, AZ (United States)] [and others

    1994-09-01

    We describe a case of ANLL with an unusual cytogenetic finding. The patient is a 73-year-old male whose bone marrow showed 100% blasts. Immunophenotyping by flow cytometry found the cells to be positive for CD15, CD33, CD34, CD38, and HLA-DR. All metaphases analyzed had trisomy 8 and an identical large amount of unidentified chromosomal material incorporated at the telomere of one of three chromosomes: 47,XY,add(20)(q13.3)[15]/47,XY,add(12)(q24.3)[3]/47,XY,add(3)(p26)[2]. This may be a jumping addition, a variation of a jumping translocation with an unknown donor, or maybe an HSR with variable sites of integration. FISH results are presented to attempt to answer the question.

  7. Trisomy 13: a rare case of congenital tarsal kink.

    Science.gov (United States)

    Lucci, Lucia M; Fukumoto, Walter K; Alvarenga, Lênio S

    2003-09-01

    We describe the management of the eyelid anomaly associated with Patau syndrome. Trisomy 13 is the genotype of the syndrome's phenotype. The eyelid anomaly was a tarsal kink, a congenital malformation of the tarsus that causes entropion. A 2-month-old white girl presented with unilateral upper eyelid entropion and central corneal ulceration. To correct this condition, two 6-0 polyglactin sutures were passed through the gray line of the upper and lower eyelids and tied. Correction of the entropion and improvement in the corneal condition were achieved after surgery. No recurrence of the entropion or corneal ulceration was noted after 2 months of follow-up. This simple technique, which corrected the eyelid malposition, providing an excellent cosmetic result without incision of the tarsus, has been previously reported in other cases of tarsal kink but not in a patient with Patau syndrome. PMID:14506431

  8. Investigating and correcting plasma DNA sequencing coverage bias to enhance aneuploidy discovery.

    Directory of Open Access Journals (Sweden)

    Dineika Chandrananda

    Full Text Available Pregnant women carry a mixture of cell-free DNA fragments from self and fetus (non-self in their circulation. In recent years multiple independent studies have demonstrated the ability to detect fetal trisomies such as trisomy 21, the cause of Down syndrome, by Next-Generation Sequencing of maternal plasma. The current clinical tests based on this approach show very high sensitivity and specificity, although as yet they have not become the standard diagnostic test. Here we describe improvements to the analysis of the sequencing data by reducing GC bias and better handling of the genomic repeats. We show substantial improvements in the sensitivity of the standard trisomy 21 statistical tests, which we measure by artificially reducing read coverage. We also explore the bias stemming from the natural cleavage of plasma DNA by examining DNA motifs and position specific base distributions. We propose a model to correct this fragmentation bias and observe that incorporating this bias does not lead to any further improvements in the detection of fetal trisomy. The improved bias corrections that we demonstrate in this work can be readily adopted into existing fetal trisomy detection protocols and should also lead to improvements in sub-chromosomal copy number variation detection.

  9. Investigating and correcting plasma DNA sequencing coverage bias to enhance aneuploidy discovery.

    Science.gov (United States)

    Chandrananda, Dineika; Thorne, Natalie P; Ganesamoorthy, Devika; Bruno, Damien L; Benjamini, Yuval; Speed, Terence P; Slater, Howard R; Bahlo, Melanie

    2014-01-01

    Pregnant women carry a mixture of cell-free DNA fragments from self and fetus (non-self) in their circulation. In recent years multiple independent studies have demonstrated the ability to detect fetal trisomies such as trisomy 21, the cause of Down syndrome, by Next-Generation Sequencing of maternal plasma. The current clinical tests based on this approach show very high sensitivity and specificity, although as yet they have not become the standard diagnostic test. Here we describe improvements to the analysis of the sequencing data by reducing GC bias and better handling of the genomic repeats. We show substantial improvements in the sensitivity of the standard trisomy 21 statistical tests, which we measure by artificially reducing read coverage. We also explore the bias stemming from the natural cleavage of plasma DNA by examining DNA motifs and position specific base distributions. We propose a model to correct this fragmentation bias and observe that incorporating this bias does not lead to any further improvements in the detection of fetal trisomy. The improved bias corrections that we demonstrate in this work can be readily adopted into existing fetal trisomy detection protocols and should also lead to improvements in sub-chromosomal copy number variation detection.

  10. Detection of chromosome aneuploidy in breast lesions with fluorescence in situ hybridization: Comparison of whole nuclei to thin tissue sections and correlation with flow cytometric DNA analysis

    Energy Technology Data Exchange (ETDEWEB)

    Visscher, D.W.; Wallis, T.; Ritchie, C.A. [Wayne State Univ., Detroit, MI (United States)

    1995-09-01

    We compared flow-cytometric DNA histogram pattern to counts of 4 fluorescent-labelled centromeric probes (chromosomes 1, 7, 8, and 17) in whole nuclei (WN) and in nuclei from formalin-fixed deparaffinized thin tissue section (TS) in 25 breast lesions. In benign lesions, signal gains (i.e., trisomic nuclei) were never observed in greater than 10% of nuclei from either WN or TS preparations. Loss of signal in benign breast lesions, however, varied considerably (0-43%) between individual case and between chromosome probes. The mean incidence of signal loss in WN of benign lesions ranged from 8.9% (chromosome 7) to 14.4 % (chromosome 1) of nuclei. These signal loss frequencies exceeded those of benign lymphoid control cells. In three benign lesions, signal loss in WN (with one probe) was observed in at least 25% of nuclei. Signal losses in benign TS, on average, were 50-150% greater than in matched WN preparations (chromosome 1: 21.7%, chromosome 7: 21.5%). Malignant lesions generally, but not always, displayed fewer monosomic nuclei and more trisomic nuclei in compared to TS, compatible with a slicing (i.e., nuclear truncation) artifact. Signal counts in carcinomas correlated well with flow cytometric DNA index; however, they were also characterized by evidence of genetic instability, manifest as signal gains in a subset of nuclei (10-25%) with individual probes in diploid range cases, as well as intratumoral heterogeneity, reflected as discrepancies in probe counts between WN and TS samples. We conclude that signal losses with centromeric probes are largely, but not entirely, explained by nuclear slicing. The minimum signal loss threshold for establishment of monosomy using interphase cytogenetics is thus unclear, even in WN. Signal gains indicative of trisomy, in contrast, are reliably associated with malignancy and may reflect gross DNA aneuploidy as well as genetic instability. 10 refs., 1 fig., 3 tabs.

  11. 孕中晚期21三体产前诊断的结果分析%Analysis of prenatal diagnosis of trisomy 21 in mid - pragnance and late pregnance

    Institute of Scientific and Technical Information of China (English)

    张晶; 李卫凯; 谢志威; 刘楗婷; 梁齐合; 孙淑湘

    2012-01-01

    目的 通过孕中晚期21三体、18三体产前诊断的结果分析,评价孕中晚期产前诊断的价值.方法 对怀孕16 ~29周符合产前诊断条件的孕妇经知情同意后,在B超介导下对孕16 -24周孕妇行羊膜腔穿刺,抽取羊水;孕25 -29周孕妇行胎儿脐静脉穿刺,抽取脐带血,进行细胞培养,染色体核型分析.结果 在2689例产前诊断病例中发现异常核型149例,异常率为5.54%.常染色体结构异常-倒位核型43例、平衡易位18例、罗氏易位8例,常染色体非整倍体数量异常(21三体、18三体、13三体)48例,性染色体数量异常15例,性染色体结构异常12例,其它核型异常5例.常染色体非整倍体数量异常(21三体、18三体、13三体)占发现异常核型的32.2%(48/149),为主要异常核型.结论 羊水细胞、脐带血染色体核型分析是目前产前诊断21三体、18三体、13三体染色体异常胎儿必不可少的检查方法,对于预防缺陷儿出生,提高人口素质,优生优育具有十分重要的意义.%Objective: To explore clinical value of amniotic cell karyotype analysis for prenatal diagnosis. Methods; Amniotic fluid of 16 -24 pregnant weeks women were drawn, fetal umbilical cord blood of 25 -29 pregnant weeks women were drawn from Umbilical vein via ultrasound - monitored through informed consent, amniotic cell and Umbilical cord blood cell were cultivated, karyotype were analyzed. Results; Among 2689 Cases of prenatal diagnosis, karyotype abnormalities were 149 cases, Abnormal rate was 5. 54% , of autosomal structural abnormalities, 43 cases were inversion karyotype, 18cases were balanced translocation, 8cases were Robinson translocation, 48 cases were the number of chromosome abnormality, 15 cases were sex chromosome abnormality, 12 cases were sex chromosome structural abnormalities, 5 case was other karyotype abnormalities. Autosomal aneuploidy number of abnormalities (triso-my21, trisomy 18, trisomy 13) account for 32. 2

  12. Trisomy 7 CVS mosaicism: Pregnancy outcome, placental and DNA analysis in 14 cases

    Energy Technology Data Exchange (ETDEWEB)

    Kalousek, D.K.; Langlois, S.; Robinson, W.P. [Univ. of British Columbia, Vancouver (Canada)] [and others

    1996-11-11

    Prenatal diagnosis by chorionic villus sampling (CVS) documents placental chromosomal mosaicism in approximately 2% of viable pregnancies at 9-12 weeks of gestation and can involve various chromosomes and placental cell lineages. Confined placental mosaicism (CPM) is the result of postzygotic mitotic errors occurring in either diploid or trisomic zygotes. With trisomic zygote rescue, depending on the parental origin of the chromosome which is lost, uniparental disomy (UPD) or biparental disomy (BPD) may arise. In this paper, we present 14 pregnancies which were diagnosed by CVS as mosaic trisomy 7. All follow-up amniocenteses showed a normal diploid karyotype. Using both classical cytogenetics and interphase analysis, studies of term placentae showed variable levels of trisomy 7. DNA analysis was performed in nine cases to determine whether the diploid fetus had BPD 7 or UPD 7. Fetal UPD 7 was present only in one case; in eight other cases biparental inheritance was demonstrated. DNA analysis to establish the origin of trisomy 7 in the placenta was fully informative in six cases. One trisomy resulted from a meiotic error and was associated with fetal UPD 7, while the rest were somatic in origin. It is difficult to compare the effect of CPM for trisomy 7 to other trisomies confined to the placenta, as for most chromosomes there are few available cases. It appears that intrauterine fetal growth is not greatly affected by the presence of a trisomy 7 cell line in the placenta. This finding is in contrast to the serious effect of high levels of trisomy 16 within the placenta on fetal intrauterine growth in a series of well-documented cases of CPM 16. 36 refs., 1 tab.

  13. Clinical presentation of mosaic trisomy 13 with longer life expectancy. Case report.

    OpenAIRE

    Gabriel Abudinén A.; Alejandra Vergara V.; Alex Castet A.; Gabriela Flores F.; Ignacio Cabrera-Samith

    2013-01-01

    INTRODUCTION: Trisomy of chromosome 13, also known as Patau Syndrome, is a genetic disorder resulting from a supernumerary chromosome 13. It was discovered in 1960 by Patau and is currently reported less frequent trisomy in humans. It is usually associated with a maternal rather than paternal meiotic disorder and, like Down syndrome, its incidence increases with maternal age. Affected infants die shortly after birth, mostly before 3 months old. It is believed that 80-90% of affected fetuses d...

  14. Gestational age at biochemical sampling in first trimester screening for trisomy 18 and 13

    DEFF Research Database (Denmark)

    Petersen, Olav Bjørn; Ekelund, Charlotte; Kirkegaard, Ida;

    Objective: To determine if gestational age at serum sampling affect the discriminative value of PAPP-A and free β hCG in relation to trisomy 18 (T18) and trisomy 13 (T13). Methods: We retrospectively searched for T18 and T13 cases in the Astraia database at two large Fetal Medicne Centres......, 39 pregnancies with trisomy 18 and 26 pregnancies with trisomy 13 was identified. We found that PAPP-A MoM levels in trisomy 18 pregnancies are less discriminatory (P = 0.0004) at earlier gestations than they are at later gestations. They decrease from an estimated median MoM of 0.54 (95% CI: 0.......16 to 0.30) at the middle of week 12. For trisomy 13 pregnancies we also found a trend, though not statistically significant, towards poorer discrimination at early gestations. In the prospective, two sample data, a total of 5 T18 and 3 T13 cases was identified. The within-case MoM-variation showed...

  15. The association between environmental exposure to pyrethroids and sperm aneuploidy.

    Science.gov (United States)

    Radwan, Michał; Jurewicz, Joanna; Wielgomas, Bartosz; Piskunowicz, Marta; Sobala, Wojciech; Radwan, Paweł; Jakubowski, Lucjusz; Hawuła, Wanda; Hanke, Wojciech

    2015-06-01

    The aim of the present study is to determine whether the environmental exposure to pyrethroids was associated with males sperm chromosome disomy. The study population consisted of 195 men who attended the infertility clinic for diagnostic purposes and who had normal semen concentration of 20-300×10(6) mL(-1) or slight oligozoospermia (semen concentration of 15-20×10(6) mL(-1)) (WHO, 1999). Participants were interviewed and provided a semen sample. The pyrethroids metabolites: 3-phenoxybenzoic acid (3PBA), cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (CDCCA), trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (TDCCA) and cis-2,2-dibromovinyl-2,2-dimethylcyclopropane-1-carboxylic acid (DBCA) were analysed in the urine using a validated gas chromatography ion-tap mass spectrometry method. Sperm aneuploidy was assessed using multicolor FISH (DNA probes specific for chromosomes X, Y, 18, 13, 21). Our results showed that CDCCA >50th percentile was associated with disomy of chromosome 18 (p=0.05) whereas the level of TDCCA in urine >50th percentile was related to XY disomy (p=0.04) and disomy of chromosome 21 (p=0.05). Urinary 3PBA level ⩽50 and >50 percentile was related to disomy of sex chromosomes: XY disomy (p=0.05 and p=0.02 respectively), Y disomy (p=0.04 and 0.02 respectively), disomy of chromosome 21 (p=0.04 and p=0.04 respectively) and total disomy (p=0.03 and p=0.04 respectively). Additionally disomy of chromosome 18 was positively associated with urinary level of 3PBA >50 percentile (p=0.03). The results reported here are found that pyrethroids may be a sperm aneugens. These findings may be of concern due to increased pyrethroid use and prevalent human exposure.

  16. Retinoic acid-treated pluripotent stem cells undergoing neurogenesis present increased aneuploidy and micronuclei formation.

    Directory of Open Access Journals (Sweden)

    Rafaela C Sartore

    Full Text Available The existence of loss and gain of chromosomes, known as aneuploidy, has been previously described within the central nervous system. During development, at least one-third of neural progenitor cells (NPCs are aneuploid. Notably, aneuploid NPCs may survive and functionally integrate into the mature neural circuitry. Given the unanswered significance of this phenomenon, we tested the hypothesis that neural differentiation induced by all-trans retinoic acid (RA in pluripotent stem cells is accompanied by increased levels of aneuploidy, as previously described for cortical NPCs in vivo. In this work we used embryonal carcinoma (EC cells, embryonic stem (ES cells and induced pluripotent stem (iPS cells undergoing differentiation into NPCs. Ploidy analysis revealed a 2-fold increase in the rate of aneuploidy, with the prevalence of chromosome loss in RA primed stem cells when compared to naïve cells. In an attempt to understand the basis of neurogenic aneuploidy, micronuclei formation and survivin expression was assessed in pluripotent stem cells exposed to RA. RA increased micronuclei occurrence by almost 2-fold while decreased survivin expression by 50%, indicating possible mechanisms by which stem cells lose their chromosomes during neural differentiation. DNA fragmentation analysis demonstrated no increase in apoptosis on embryoid bodies treated with RA, indicating that cell death is not the mandatory fate of aneuploid NPCs derived from pluripotent cells. In order to exclude that the increase in aneuploidy was a spurious consequence of RA treatment, not related to neurogenesis, mouse embryonic fibroblasts were treated with RA under the same conditions and no alterations in chromosome gain or loss were observed. These findings indicate a correlation amongst neural differentiation, aneuploidy, micronuclei formation and survivin downregulation in pluripotent stem cells exposed to RA, providing evidence that somatically generated chromosomal

  17. 18-三体综合征胎儿超声指标分析%Ultrasound findings associated with fetuses of trisomy 18 syndrome

    Institute of Scientific and Technical Information of China (English)

    邵明焕; 邓学东; 钱孝纲

    2012-01-01

    Objective To assess the sonographic appearances of trisomy 18 and the clinical significance of prenatal ultrasonic dignosis of trisomy 18. Methods The ultrasound findings as trisomy 18 by karyotyping were evaluated. Results Sixteen of 19 fetuses had at least two deteceted abnormalities. Fetal cardiac anomalies were the most common findings followed by abnormal hand posturing. Other common sonographic findings included choroid plexus cysts, omphalocele, Dandy-Walker syndrome, cleft lip, esophageal atresia, micrognathia, club foot, diaphragmatic hernia, and single umbilical artery. Conclusion The evaluation of ultrasound findings is effective for prenatal screening in the fetus with trisomy 18 during the second and third trimester.%目的 探讨18-三体综合征胎儿的声像特征及产前超声诊断的临床意义.方法 回顾分析经羊水穿刺或脐血穿刺胎儿染色体检查确诊为18-三体综合征的胎儿声像特征.结果 19例18-三体综合征16例有两个及以上异常声像表现.最常见异常为心脏畸形(9例),其次为手畸形(5例),再其次为脉络丛囊肿,脐膨出,Dandy-Walker综合征,唇裂,食道闭锁,小颌畸形,足内翻,膈疝,单脐动脉等.结论 中、晚孕期超声筛查是提高产前检出18-三体综合征的有效措施.

  18. Retrospective study of trisomy 18 in chorionic villi with fluorescent in situ hybridization on archival direct preparations

    OpenAIRE

    Van Opstal, Diane; Berg, Cardi; Jahoda, M.; Brandenburg, Helen; Los, F.J.; in't Veld, Peter

    1995-01-01

    textabstractTrisomy 18 in direct chorionic villus preparations needs further investigation since the chromosome abnormality may be confined to the placenta and may not represent the actual fetal karyotype. We performed, retrospectively, fluorescent in situ hybridization (FISH) with the chromosome 18 centromere probe (L1.84) on interphase nuclei of destained slides of all cases of full trisomy 18 (n=22) and mosaic trisomy 18 (n=8) detected among 7600 first-trimester chorionic villus samples du...

  19. Nine children over the age of one year with full trisomy 13: a case series describing medical conditions.

    Science.gov (United States)

    Bruns, Deborah A; Campbell, Emily

    2014-12-01

    Trisomy 13 (Patau syndrome), identified by Patau and colleagues [1960; Lancet 1: 790-793] is the third most common autosomal condition. Population studies indicate less than one in 10 children reaches their first birthday. In the face of mixed findings and recommendations for treatment, additional research is needed to further determine what contributes to longevity and implications for treatment for presenting medical conditions. The purpose of the present study is to report on presenting medical conditions and the presence or absence of the specific conditions (age at survey completion). Data on nine survivors (seven female, two male) with trisomy 13 indicated mean gestational age of approximately 36 weeks, birth weight ranging from 1100 to 3290 g and mean length of 45.3 cm. Length of hospital stay after birth varied. The majority of infants presented with well-known physical characteristics. Medical conditions and their treatment varied at birth and at survey completion. Notably, several infants' cardiac anomalies resolved without surgical intervention. Surgeries were provided for a range of conditions including gastrostomy tube placement to address feeding issues and removal of intestinal blockage. There were no reports of holoprosencephaly. Implications and recommendations are provided. PMID:25323598

  20. Polimorfisme Gen Apolipoprotein E Pada Penderita Sindrom Down Trisomi 21

    Directory of Open Access Journals (Sweden)

    Malinda Meinapuri

    2013-01-01

    Full Text Available AbstrakLatar Belakang: Sindrom Down merupakan suatu kelainan kromosom yang ditandai dengan adanya baik seluruhnya (trisomi 21 maupun sebagian (translokasi suatu salinan tambahan kromosom ke 21. Apolipoprotein E (APOE merupakan suatu bentuk protein polimorfik yang disandikan oleh suatu gen yang berlokasi pada lengan panjang kromosom 19 pada posisi 13.2 (19q13.2. Polimorfism gen APOE berkaitan dengan meningkatnya frekuensi alel ε4 yang berakibat terjadinya hambatan dalam percabangan dan pertumbuhan neuron. Dimungkinkan, penderita Sindrom Down Trisomi 21 memiliki gen APOE yang berbeda dengan kontrol sebagai faktor yang dapat mengakibatkan penuaan dini otak. Metode : Penelitian ini merupakan penelitian kasus kontrol untuk mengamati perbedaan distribusi dan frekuensi alel dan genotip gen APOE pada penderita Sindrom Down trisomi 21 dibandingkan dengan kontrol. Kasus Sindrom Down dan kontrol diambil dari data sekunder yang tersimpan di Center for Biomedical Research (CEBIOR Semarang Indonesia. Ekstraksi DNA dilakukan dengan menggunakan metode yang terdapat di (CEBIOR Semarang Indonesia. Kegiatan selanjutnya adalah pemeriksaan polimorfisme gen Apolipoprotein E dengan mengunakan teknik PCR dan RFLP. Hasil : Sebanyak 33 sampel dari penderita Sindrom Down, 18 laki-laki dan 15 perempuan dan 33 sampel kontrol, 18 laki-laki dan 15 perempuan. Baik sampel Sindrom Down maupun kontrol memiliki frekuensi alel ε3 paling tinggi dibandingkan dengan alel ε2 dan ε4. Pada Sindrom Down didapatkan alel ε4 4 sampel (6,1% dan alel ε2 8 sampel (12,1%. Baik sampel Sindrom Down maupun kontrol memiliki genotip ε3/ε3 paling tinggi dibandingkan dengan genotip gen APOE lainnya. Pada Sindrom Down didapatkan genotip ε2/ε4 4 sampel (12,1% dan genotip ε2/ε2 2 sampel (6,1%. Simpulan : Terdapat perbedaan distribusi alel dan genotip gen APOE pada penderita Sindrom Down trisomi 21 dibandingkan dengan kelompok kontrol. Diperlukan analisis sampel yang lebih banyak untuk

  1. Muscular and other abnormalities in a case of Edwards' syndrome (18-trisomy).

    Science.gov (United States)

    Aziz, M A

    1979-10-01

    This paper describes the anatomical variations observed in a specimen exhibiting Edwards' Syndrome (18-trisomy). The clinical and autopsy data are compared with those reported in earlier literature. Aside from having a tracheoesophageal fistula, the viscera were characterized by abnormalities of the heart, lungs, liver and kidneys. The facial musculature was relatively undifferentiated. Only a few abnormalities were recorded in the otomandibular and suprahyoid structures. The infrahyoid region had three pairs of supernumerary muscles, including the "sternohyoideus azygos." The bluk of abnormalities were found in the muscles and nerves of the upper limb. These included the absence of the palmaris longus and brevis, the subclavius and the extensor digiti quinti proprius; the presence of supernumerary muscles, e.g., the "rhomboideus occipitalis," the "latissimocondyloideus," and the "subclavius posticus." The deltoid and the pectoralis major were fused to form the "deltopectoral" complex. A definitive musculocutaneous nerve was found in the right arm only. In the lower extremity supernumerary muscles included the "tenuissimus," "peroneus quinti digiti," and the "extensor primi internodii hallucis." PMID:524303

  2. Fetal Nasal Bone Status In Iranian Women Undergoing First-Trimester Screening For Trisomy 21: A Review and an Observational Study.

    Directory of Open Access Journals (Sweden)

    Poureisa

    2015-08-01

    Full Text Available Background Failed visualization of the fetal nasal bone (NB by ultrasound at 11 - 14 weeks of gestation is strongly associated with chromosomal abnormalities. Meanwhile, the incidence of the absent fetal NB in normal fetuses in the first trimester in mothers of different ethnic origins differs significantly. It is, therefore, important to assess ethnic variations in the first-trimester visualization of the fetal NB before introducing this marker into routine screening programs for aneuploidy. Objectives The objectives of this study were to determine the NB length and the prevalence of the NB absence as well as calculating the likelihood ratio (LR for the absence of the NB in normal fetuses of Iranian women undergoing first-trimester screening for trisomy 21. Patients and Methods In 767 normal fetuses, the fetal profile was examined by ultrasound for the absence/presence of the NB. The NB length was also measured, and the LR for the NB absence was also determined. Results The NB was absent in 2/767 (0.26% of the fetuses. The mean length of the NB was 3.6 ± 0.69 mm for the fetuses of 11 - 14 weeks gestational age. The LR value of the absent NB was equal to 250 in the normal fetuses of the Iranian population living in the North-West provinces. Conclusion The low prevalence of the NB absence in normal fetuses in the present study is compatible with the larger size of the NB in Iranian people compared to other communities. Meanwhile, the reference range of the NB length in normal Iranian fetuses was established so that basic data could be recorded for further studies regarding the absence or presence of the NB in screening for chromosomal abnormalities (Down syndrome within the Iranian population.

  3. Increased expression of BubR1 protects against aneuploidy and cancer and extends healthy lifespan

    NARCIS (Netherlands)

    Baker, Darren J.; Dawlaty, Meelad M.; Wijshake, Tobias; Jeganathan, Karthik B.; Malureanu, Liviu; van Ree, Janine H.; Crespo-Diaz, Ruben; Reyes, Santiago; Seaburg, Lauren; Shapiro, Virginia; Behfar, Atta; Terzic, Andre; van de Sluis, Bart; van Deursen, Jan M.

    2013-01-01

    The BubR1 gene encodes for a mitotic regulator that ensures accurate segregation of chromosomes through its role in the mitotic checkpoint and the establishment of proper microtubule-kinetochore attachments. Germline mutations that reduce BubR1 abundance cause aneuploidy, shorten lifespan and induce

  4. Re: Fluorescence In Situ Hybridization Detects Increased Sperm Aneuploidy in Men with Recurrent Pregnancy Loss

    Directory of Open Access Journals (Sweden)

    Ranjith Ramasamy,

    2015-06-01

    Full Text Available Male factor infertility can be overcome with the use of assisted reproductive technologies and for this purpose the mostly intracytoplasmic sperm injection (ICSI was used. Although using sperm from men with relatively normal semen parameters with high-tech methods, many couples fail to achieve pregnancy or face recurrent pregnancy loss (RPL. In this study, the authors tried to find an answer for potential causes of RPL and in vitro fertilization (IVF failure by using fluorescence in situ hybridization (FISH analysis. FISH analysis was used to detect numerical abnormalities in sex chromosomes (X,Y and autosomes (13,18, 21 in ejaculated sperm. Significantly higher percentage of sperm aneuploidy was found in men with RPL within the sex chromosomes and chromosomes 18,13 and 21. Although men with normal sperm parameter, 40% of abnormal sperm aneuploidy was found in all the chromosomes analyzed. In addition to that, men with abnormal sperm density and motility had a higher percentage of sex chromosome aneuploidy than men with normal density and motility. In conclusion, sperm FISH analysis can be suggested in men with RPL and normal sperm density/motility to understand the reason of pregnancy failure. Also, this study showed that men with oligoasthenoteratozoospermia (OAT might have a greater percentage of sperm aneuploidy compared to those with normal sperm parameters.

  5. Effects of Sex Chromosome Aneuploidies on Brain Development: Evidence from Neuroimaging Studies

    Science.gov (United States)

    Lenroot, Rhoshel K.; Lee, Nancy Raitano; Giedd, Jay N.

    2009-01-01

    Variation in the number of sex chromosomes is a relatively common genetic condition, affecting as many as 1/400 individuals. The sex chromosome aneuploidies (SCAs) are associated with characteristic behavioral and cognitive phenotypes, although the degree to which specific individuals are affected can fall within a wide range. Understanding the…

  6. Incidental prenatal diagnosis of sex chromosome aneuploidies: health, behavior, and fertility.

    NARCIS (Netherlands)

    Pieters, J.J.; Kooper, A.J.A.; Geurts van Kessel, A.H.M.; Braat, D.D.M.; Smits, A.P.T.

    2011-01-01

    Objective. To assess the diagnostic relevance of incidental prenatal findings of sex chromosome aneuploidies. Methods. We searched with medical subject headings (MeSHs) and keywords in Medline and the Cochrane Library and systematically screened publications on postnatally diagnosed sex chromosomal

  7. Low aneuploidy rate in early pregnancy loss abortuses from patients with polycystic ovary syndrome.

    Science.gov (United States)

    Wang, Qiong; Luo, Lu; Lei, Qiong; Lin, Ming-Mei; Huang, Xuan; Chen, Ming-Hui; Zeng, Yan-Hong; Zhou, Can-Quan

    2016-07-01

    A prospective cohort study was conducted to determine whether chromosome aneuploidy increases the risk of early spontaneous abortions in patients with polycystic ovary syndrome (PCOS). A total of 1461 patients who conceived after IVF and embryo transfer were followed; 100 patients who had experienced clinical spontaneous abortion were recruited, 32 with PCOS and 68 without PCOS. Before 2013, genetic analysis comprised conventional cultured villus chromosome karyotyping and a multiplex ligation-dependent probe amplification subtelomere assay combined with fluorescence in-situ hybridization; since 2013, array-based comparative genomic hybridization technique combined with chromosome karyotyping has been used. Age, BMI, pregnancy history, gestational age and total gonadotrophin dosage did not differ significantly between the PCOS and non-PCOS groups. In the PCOS group, 28.1% of abortuses demonstrated aneuploidy, which was significantly lower (P = 0.001) than in the non-PCOS group (72.1%). Further statistical analyses controlling for maternal age demonstrated that abortuses of women with PCOS were significantly less (P = 0.001) likely to have chromosome aneuploidy. Embryonic aneuploidy does not play a vital role in early spontaneous abortion in women with PCOS. Maternal factors resulting in endometrial disorders are more likely to be responsible for the increased risk of early spontaneous abortion in patients with PCOS. PMID:27157933

  8. Progesterone facilitates chromosome instability (aneuploidy) in p53 null normal mammary epithelial cells

    Science.gov (United States)

    Goepfert, T. M.; McCarthy, M.; Kittrell, F. S.; Stephens, C.; Ullrich, R. L.; Brinkley, B. R.; Medina, D.

    2000-01-01

    Mammary epithelial cells from p53 null mice have been shown recently to exhibit an increased risk for tumor development. Hormonal stimulation markedly increased tumor development in p53 null mammary cells. Here we demonstrate that mammary tumors arising in p53 null mammary cells are highly aneuploid, with greater than 70% of the tumor cells containing altered chromosome number and a mean chromosome number of 56. Normal mammary cells of p53 null genotype and aged less than 14 wk do not exhibit aneuploidy in primary cell culture. Significantly, the hormone progesterone, but not estrogen, increases the incidence of aneuploidy in morphologically normal p53 null mammary epithelial cells. Such cells exhibited 40% aneuploidy and a mean chromosome number of 54. The increase in aneuploidy measured in p53 null tumor cells or hormonally stimulated normal p53 null cells was not accompanied by centrosome amplification. These results suggest that normal levels of progesterone can facilitate chromosomal instability in the absence of the tumor suppressor gene, p53. The results support the emerging hypothesis based both on human epidemiological and animal model studies that progesterone markedly enhances mammary tumorigenesis.

  9. 应用多重连接依赖探针扩增技术快速检测胎儿染色体非整倍体与结构异常%Application of multiplex ligation-dependent probe amplification for rapid detection of aneuploidies and structural chromosomal abnormalities in prenatal diagnosis

    Institute of Scientific and Technical Information of China (English)

    张菁菁; 胡平; 罗春玉; 季修庆; 周静; 刘安; 马定远; 许争峰

    2014-01-01

    目的 探讨多重连接依赖探针扩增(multiplex ligation-dependent probe amplification,MLPA)技术在羊水细胞染色体非整倍体及染色体结构异常检测中的应用.方法 应用MLPA技术对286份羊水样本进行检测,并与常规染色体核型分析进行对比,对于检测到的染色体结构异常应用微阵列比较基因组杂交技术(array comparative genomic hybridization,aCGH)进行验证.结果 在286份羊水中,共检测到10例21-三体,2例18三体,1例13三体,1例嵌合21-三体,1例X单体,1例X染色体短臂大片段缺失,1例18号染色体短臂部分三体,1例18号染色体长臂和短臂大片段缺失.所有MLPA结果与染色体核型分析均一致.对于检测到的染色体结构异常均应用aCGH技术验证,检测结果符合率100%.结论 MLPA可快速检出常见染色体非整倍体以及染色体结构异常包括大片段缺失与重复,为临床产前诊断提供有价值的信息.%Objective To explore the value of multiplex ligation-dependent probe amplification (MLPA) for rapid detection of aneuploidies and structural chromosomal abnormalities during prenatal diagnosis.Methods Two hundred and eight six amniotic fluid samples were analyzed with both MLPA and conventional karyotyping.Structural abnormalities were verified with array comparative genomic hybridization.Results Ten cases of trisomy 21,2 cases of trisomy 18,1 case of trisomy 13,1 case of mosaic trisomy 21,1 case of 45,X,1 case of large deletion of Xp,1 case of trisomy 18p and 1 case of large deletion of 18p and 18q were identified.The same results were derived by both MLPA and conventional karyotyping.Structural abnormalities were verified by array comparative genomic hybridization (aCGH)with 100% accuracy.Conclusion In addition to aneuploidies,MLPA can rapidly identify large deletions and duplications of chromosomes 21,18,13,X and Y.MLPA is supplementary to conventional karyotyping for identification of such chromosomal abnormalities

  10. Mouse models of cognitive disorders in trisomy 21: a review.

    Science.gov (United States)

    Sérégaza, Zohra; Roubertoux, Pierre L; Jamon, Marc; Soumireu-Mourat, Bernard

    2006-05-01

    Trisomy 21 (TRS21) is the most frequent genetic cause of mental retardation. Although the presence of an extra copy of HSA21 is known to be at the origin of the syndrome, we do not know which 225 HSA21 genes have an effect on cognitive processes. Mouse models of TRS21 have been developed using syntenies between HSA21 and MMU16, MMU10 and MMU17. Available mouse models carry extra fragments of MMU16 or of HSA21 that cover all of HSA21 (chimeric HSA21) or MMU16 (Ts16); some carry large parts of MMU16 (Ts65Dn, Ts1Cje, Ms1Cje), while others have reduced contiguous fragments covering the D21S17-ETS2 region or single transfected genes. This offers a nest design strategy for deciphering cognitive (learning, memory and exploration) and associated brain abnormalities involving each of these chromosomal regions. This review confirms the crucial but not exclusive contribution of the D21S17-ETS2 region encompassing 16 genes to cognitive disorders. PMID:16523244

  11. "How should I tell my child?" Disclosing the diagnosis of sex chromosome aneuploidies.

    Science.gov (United States)

    Dennis, Anna; Howell, Susan; Cordeiro, Lisa; Tartaglia, Nicole

    2015-02-01

    To date, the disclosure of a sex chromosome aneuploidy (SCA) diagnosis to an affected individual has not been explored. This study aimed to assess the timing and content revealed to an affected child by his or her parent(s), resources accessed in preparation, parental feelings of preparedness, common parental concerns, and recommendations for disclosure approaches. Two online surveys were created: 1) for parents of a child with a diagnosis and 2) for individuals with a diagnosis. One-hundred thirty-nine parent surveys (XXY n = 68, XXX n = 21, XYY n = 9, other SCAs n = 41) and 67 individual surveys (XXY n = 58, XXX n = 9) were analyzed. Parents most frequently discussed the topics of learning disabilities (47 %) and genetics (45 %) with their child during the initial disclosure. A significantly greater proportion of parent respondents reported feeling prepared vs. unprepared for disclosure, regardless of their child's diagnosis (z-test of proportions, all p's < 0.001). Both prepared and unprepared parents most frequently accessed resources such as websites, support groups, and discussion with the child's physician prior to disclosure, with unprepared parents accessing fewer resources (M = 2.0 ± 1.41) than prepared parents [M = 2. ± 1.56; t(101) =-2.02, p < 0.05]. Common parental concerns included making the conversation age-appropriate, discussing infertility, and possible impact on the child's self-esteem. Both parent and individual respondents endorsed being honest with the child, disclosing the diagnosis early and before puberty, and discussing the diagnosis gradually over time. These results provide recommendations for parents, and suggest benefits from additional resources and supports to alleviate concerns when approaching diagnosis disclosure.

  12. Partial trisomy 13q identified by sequential fluorescence in situ hybridization

    Energy Technology Data Exchange (ETDEWEB)

    Gopal Rao, V.V.N.; Carpenter, N.J.; Gucsavas, M. [Institute of Medical Genetics, Tulsa, OK (United States)] [and others

    1995-07-31

    We report on a 19-month-old boy with partial trisomy 13q resulting from a probable balanced translocation involving chromosomes 1 and 13. The infant presented with omphalocele, malrotation, microcephaly with overriding skull bones, micrognathia, apparently low-set ears, rocker-bottom feet, and congenital heart disease, findings suggestive of trisomy 13. Karyotypic studies from peripheral blood lymphocytes documented an unbalanced karyotype 46,XY,-1,+der. The mother`s chromosomes were normal, and the father was not available. Conventional cytogenetic techniques were unable to identify the extra material on the terminal 1q. Using fluorescence in situ hybridization (FISH) on the GTL-banded metaphases, the extra material on 1q was identified as the terminal long arm of 13, thus resulting in partial trisomy 13 (q32-qter). 8 refs., 2 figs., 1 tab.

  13. Trisomy 8: a common finding in mouse embryonic stem (ES cell lines

    Directory of Open Access Journals (Sweden)

    Kim Young Mi

    2013-01-01

    Full Text Available Abstract Background Obtaining a germ cell line is one of the most important steps in developing a transgenic or knockout mouse with a targeted mutated gene of interest. A common problem with this technology is that embryonic stem (ES cells often lack, or are extremely inefficient at, germ line transmission. Results To determine whether chromosomal anomalies are correlated with inefficient ES cell germ line transmission, we examined 97 constructed ES cell lines using conventional cytogenetic analysis, and fluorescence in situ hybridization (FISH. Chromosomal abnormalities occurred in 44 (45% out of the 97 specimens analyzed: 31 specimens had trisomy 8 or mosaic trisomy 8, eight specimens had partial trisomy 8 resulting from unbalanced translocations, and five specimens had other chromosomal anomalies. Conclusions Our data suggest that chromosomal analysis is an important tool for improving the yield and quality of gene targeting experiments.

  14. Aberrant “Barbed-Wire” Nuclear Projections of Neutrophils in Trisomy 18 (Edwards Syndrome

    Directory of Open Access Journals (Sweden)

    Basil M. Kahwash

    2015-01-01

    Full Text Available We discuss the significance of neutrophils with increased, aberrant nuclear projections mimicking “barbed-wire” in a newborn child with trisomy 18 (T18. Increased, aberrant nuclear projections have been previously reported in trisomy of the D group of chromosomes (chromosomes 13, 14, and 15, and we report similar findings in a patient with T18. The peripheral blood smear showed relative neutrophilia with the majority (37% of neutrophils showing two or more thin, rod-shaped or spike-shaped, and often pedunculated aberrant nuclear projections. The number of projections ranged from 2 to 6 per cell, averaged 2 per affected neutrophil, and ranged in length from 0.22 μm to 0.83 μm. This case confirms that the morphologic finding described is not restricted to trisomy of one of the chromosomes in group D, as implied in the literature.

  15. Trisomy 8 in Pediatric Acute Myeloid Leukemia. A NOPHO-AML Study

    DEFF Research Database (Denmark)

    Laursen, Anne Cathrine Lund; Sandahl, Julie Damgaard; Kjeldsen, Eigil;

    2016-01-01

    Trisomy 8 (+8) is a common cytogenetic aberration in acute myeloid leukemia (AML); however, the impact of +8 in pediatric AML is largely unknown. We retrospectively investigated 609 patients from the NOPHO-AML database to determine the clinical and cytogenetic characteristics of +8 in pediatric AML......;11). Trisomy 8 alone was associated with older age (median age 10.1 years), FAB M2 (33%), and FLT3-ITD mutations (58%). The 5-year event-free survival for patients with +8 alone was 50% and 5-year overall survival was 75%. In conclusion, +8 is one of the most common cytogenetic aberrations in pediatric AML...... and to investigate its prognostic impact. Complete cytogenetic data were available in 596 patients (98%) aged 0-18 years, diagnosed from 1993 to 2012, and treated according to the NOPHO-AML 1993 and 2004 protocols in the Nordic countries and Hong Kong. We identified 86 patients (14%) with +8. Trisomy 8 was combined...

  16. Genotype-phenotype correlation and pregnancy outcomes of partial trisomy 14q: A systematic review.

    Science.gov (United States)

    Bregand-White, Julia; Saller, Devereux N; Clemens, Michele; Surti, Urvashi; Yatsenko, Svetlana A; Rajkovic, Aleksandar

    2016-09-01

    Over the last decade, several advances in ultrasound techniques, increasing availability of whole genome microarray testing, and overall expansion of our knowledge about the human genome have drastically enhanced our ability to detect chromosomal abnormalities prenatally. Despite that, genotype-phenotype correlation is difficult to establish for many chromosomal aberrations, particularly for those that are rare, as it requires thorough analysis of a significant number of cases. This in turn increases the burden of the obstetric provider to appropriately counsel a patient regarding prognosis and pregnancy options in these complicated situations. Our experience in prenatal diagnosis and management of a fetus with multiple anomalies and partial trisomy for the 14q11-q24.2 prompted a comprehensive analysis of the relevant literature. Although complete non-mosaic trisomy 14 is associated with first trimester miscarriages, partial trisomy 14q is a rare condition with undefined genotype-phenotype correlation, preventing accurate prenatal counseling, and informed decision making. We performed a systematic literature review, that aimed to summarize prenatal and postnatal findings of individual case reports on 51 patients with partial trisomy 14q in order to elucidate genotype-phenotype correlation, and to supply healthcare professionals with recommendation on essential fetal and parental testing for accurate diagnosis, pregnancy outcomes, and proper family counseling. Comparison of the clinical findings among the patients with partial 14q trisomy suggest that the resulting phenotype is likely to be influenced by the extent of the 14q trisomy segment, associated chromosomal imbalances, parental origin of the rearrangement, and dosage of the genes within the imprinted 14q32 cluster. © 2016 Wiley Periodicals, Inc. PMID:27286879

  17. Two cases of Y; autosome translocations: A 45,X male and a clinically trisomy 18 patient

    Energy Technology Data Exchange (ETDEWEB)

    Farah, S.B.; Ramos, C.F.; Mello, M.P. de; Sartorato, E.L.; Lopes, V.L.G.S.; Cavalcanti, D.P.; Hackel, C. [Universidade Estadual de Campinas, SP (Brazil); Horeilli-Kuitunen, N. [Univ. of Helsinki (Finland)

    1994-02-15

    The authors report on 2 cases of Y; autosome translocations. One is a male with normal external genitalia and 45,X karyotype without evidence of mosaicism or apparent translocation on cytogenetic analysis. In situ hybridization showed that the euchromatic portion of the Y-chromosome is translocated to chromosome 15. The other case is a clinically trisomy 18 male patient, with modal number of 46, a small metacentric marker with appearance of an i(18p) and cytogenic and molecular evidence of Y;18 translocation. The occurrence of Y;18 translocation associated with clinical signs of trisomy 18 is reported here for the first time. 32 refs., 2 figs., 1 tab.

  18. Ethics is an essential dimension of first-trimester risk assessment for trisomy 21.

    Science.gov (United States)

    Chervenak, Frank A; McCullough, Laurence B

    2008-04-01

    We identify the clinical implications of the ethics of informed consent for risk assessment for trisomy 21. Based on the ethics of informed consent, we argue that routinely offering first-trimester risk assessment in centers qualified to provide it is ethically obligatory. We describe how pregnant women can be expected to respond to this offer. We then argue that routinely withholding the results of first-trimester risk assessment is ethically unjustified. The ethics of informed consent is an essential dimension of first-trimester risk assessment for trisomy 21. PMID:18450138

  19. Sensitivity of Noninvasive Prenatal Detection of Fetal Aneuploidy from Maternal Plasma Using Shotgun Sequencing Is Limited Only by Counting Statistics

    OpenAIRE

    Fan, H. Christina; Quake, Stephen R.

    2010-01-01

    We recently demonstrated noninvasive detection of fetal aneuploidy by shotgun sequencing cell-free DNA in maternal plasma using next-generation high throughput sequencer. However, GC bias introduced by the sequencer placed a practical limit on the sensitivity of aneuploidy detection. In this study, we describe a method to computationally remove GC bias in short read sequencing data by applying weight to each sequenced read based on local genomic GC content. We show that sensitivity is limited...

  20. Screening of Fetal Chromosome Aneuploidies in the First and Second Trimester of 125,170 Iranian Pregnant Women

    OpenAIRE

    Elham SEYYED-KAVOOSI; YOUNESSI, Sarang; Dariush D Farhud

    2015-01-01

    Background: Aneuploidy is one of the main causes of congenital anomalies, mental and physical disabilities, in new-borns. The aim of this study was to determine various chromosomal aneuploidies in the first and second trimester screening of pregnant women, in Iran.Methods: A descriptive retrospective study was conducted on 125,170 pregnant women referred to a major referral medical diagnostic laboratory (Niloo Laboratory, Tehran) for prenatal screening tests (2010-2013). Patients were di-vide...

  1. Clinical experience from Thailand noninvasive prenatal testing as screening tests for trisomies 21, 18 and 13 in 4736 pregnancies

    DEFF Research Database (Denmark)

    Manotaya, S.; Uerpairojkit, B.; Chen, F.;

    2016-01-01

    PurposeThe purpose of this article is to report the clinical experience and performance of massively parallel sequencing-based noninvasive prenatal testing (NIPT) as a screening method in detecting trisomy 21, 18, and 13 (T21/T18/T13) in a mixed-risk population in Thailand. MethodsIn a 30-month...... as the screening test in a large-scale mixed-risk population in Thailand for the first time. It provides the experience of implementing NIPT in a developing country with patient-funded prenatal screening system and continuous quests for applicable nationwide uptake of prenatal screening and diagnosis....... period, 121 medical centers in Thailand offered NIPT as clinical screening tests for fetal T21, T18, and T13 in the mixed-risk population. All NIPT-positive cases were recommended to undergo invasive prenatal diagnosis. ResultsA total of 4736 participants received the NIPT test, including 2840 high...

  2. [DNA aneuploidy in children with acute leukemia: II. Correlation with the phenotype of blasts, clinical picture and course of disease].

    Science.gov (United States)

    Ritter, J; Hiddemann, W; Wörmann, B; Büchner, T; Schellong, G

    1985-01-01

    Analysis of the cellular DNA content was carried out in 162 children with ALL and 34 children with AML admitted to the university children's hospital Münster between 1979 and 1984. DNA aneuploidies were identified at a similar frequency in ALL (40%) and AML (44%). However, the degree of DNA aneuploidies (DNA-index) was significantly lower in aneuploid AML (median 1.09) than in aneuploid ALL (median 1.19). We found a significantly lower incidence of DNA-aneuploidies in T-ALL (3/21; 14%) as compared to non-T/non-B-ALL (60/137; 44%). No differences were found between children with and without DNA aneuploidy in PAS score and TdT activity. In non-T/non-B-ALL DNA aneuploidy is highly correlated with a long pretherapeutic history, with a low WBC and blast count and with a low serum LDH. Under the conditions of the ALL protocols BFM-79/81 and 81/83 no difference in the remission rate was found between the two patient groups. However, more relapses occurred so far within the group of children without DNS aneuploidy. PMID:3892150

  3. Screening of Fetal Chromosome Aneuploidies in the First and Second Trimester of 125,170 Iranian Pregnant Women

    Science.gov (United States)

    SEYYED KAVOOSI, Elham; YOUNESSI, Sarang; FARHUD, Dariush D.

    2015-01-01

    Background: Aneuploidy is one of the main causes of congenital anomalies, mental and physical disabilities, in newborns. The aim of this study was to determine various chromosomal aneuploidies in the first and second trimester screening of pregnant women, in Iran. Methods: A descriptive retrospective study was conducted on 125,170 pregnant women referred to a major referral medical diagnostic laboratory (Niloo Laboratory, Tehran) for prenatal screening tests (2010–2013). Patients were divided into 3 groups: first trimester screening (FTS), second trimester screening (STS), and combined screening groups. In positive and borderline cases, and amniocentesis and cytogenetic analysis were carried out. Results: Total prevalence of aneuploidy in 125,170 pregnant women was one in 491, (Detection Rate=82.7% for Down syndrome). The DR for DS in three groups was as follow: 87.5% for FTS (25783 women), 80.9% for STS (91345 women), and 94.7% for combined tests (8042 women). Total number of cases with Edward's syndrome was 18, Patau's syndrome six, Klinefelter syndrome six, triploidy three, and Cri-du-chat syndrome one. Conclusion: The present study shows the frequency of aneuploidy in the first and second trimester screenings in a major medical laboratory in Tehran. The prevalence of aneuploidies grows with increased maternal age. The rate of aneuploidy in first trimester is higher than second. PMID:26258091

  4. Non-random aneuploidy specifies subgroups of pilocytic astrocytoma and correlates with older age.

    Science.gov (United States)

    Fontebasso, Adam M; Shirinian, Margret; Khuong-Quang, Dong-Anh; Bechet, Denise; Gayden, Tenzin; Kool, Marcel; De Jay, Nicolas; Jacob, Karine; Gerges, Noha; Hutter, Barbara; Şeker-Cin, Huriye; Witt, Hendrik; Montpetit, Alexandre; Brunet, Sébastien; Lepage, Pierre; Bourret, Geneviève; Klekner, Almos; Bognár, László; Hauser, Peter; Garami, Miklós; Farmer, Jean-Pierre; Montes, Jose-Luis; Atkinson, Jeffrey; Lambert, Sally; Kwan, Tony; Korshunov, Andrey; Tabori, Uri; Collins, V Peter; Albrecht, Steffen; Faury, Damien; Pfister, Stefan M; Paulus, Werner; Hasselblatt, Martin; Jones, David T W; Jabado, Nada

    2015-10-13

    Pilocytic astrocytoma (PA) is the most common brain tumor in children but is rare in adults, and hence poorly studied in this age group. We investigated 222 PA and report increased aneuploidy in older patients. Aneuploid genomes were identified in 45% of adult compared with 17% of pediatric PA. Gains were non-random, favoring chromosomes 5, 7, 6 and 11 in order of frequency, and preferentially affecting non-cerebellar PA and tumors with BRAF V600E mutations and not with KIAA1549-BRAF fusions or FGFR1 mutations. Aneuploid PA differentially expressed genes involved in CNS development, the unfolded protein response, and regulators of genomic stability and the cell cycle (MDM2, PLK2),whose correlated programs were overexpressed specifically in aneuploid PA compared to other glial tumors. Thus, convergence of pathways affecting the cell cycle and genomic stability may favor aneuploidy in PA, possibly representing an additional molecular driver in older patients with this brain tumor. PMID:26378811

  5. Tetraploid cells from cytokinesis failure induce aneuploidy and spontaneous transformation of mouse ovarian surface epithelial cells

    OpenAIRE

    Lv, Lei; Zhang, Tianwei; Yi, Qiyi; Huang, Yun; Wang, Zheng; Hou, Heli; Zhang, Huan; Zheng, Wei; Hao, Qiaomei; Guo, Zongyou; Howard J Cooke; Shi, Qinghua

    2012-01-01

    Most ovarian cancers originate from the ovarian surface epithelium and are characterized by aneuploid karyotypes. Aneuploidy, a consequence of chromosome instability, is an early event during the development of ovarian cancers. However, how aneuploid cells are evolved from normal diploid cells in ovarian cancers remains unknown. In the present study, cytogenetic analyses of a mouse syngeneic ovarian cancer model revealed that diploid mouse ovarian surface epithelial cells (MOSECs) experienced...

  6. Non-invasive prenatal testing for aneuploidy and beyond: challenges of responsible innovation in prenatal screening

    OpenAIRE

    Dondorp, Wybo; de Wert, Guido; Bombard, Yvonne; Bianchi, Diana W; Bergmann, Carsten; Borry, Pascal; Chitty, Lyn S; Fellmann, Florence; Forzano, Francesca; Hall, Alison; Henneman, Lidewij; Howard, Heidi C; Lucassen, Anneke; Ormond, Kelly; Peterlin, Borut

    2015-01-01

    This paper contains a joint ESHG/ASHG position document with recommendations regarding responsible innovation in prenatal screening with non-invasive prenatal testing (NIPT). By virtue of its greater accuracy and safety with respect to prenatal screening for common autosomal aneuploidies, NIPT has the potential of helping the practice better achieve its aim of facilitating autonomous reproductive choices, provided that balanced pretest information and non-directive counseling are available as...

  7. Integrating stakeholder perspectives into the translation of cell-free fetal DNA testing for aneuploidy

    OpenAIRE

    Sayres, Lauren C.; Allyse, Megan; Cho, Mildred K.

    2012-01-01

    Background The translation of novel genomic technologies from bench to bedside enjoins the comprehensive consideration of the perspectives of all stakeholders who stand to influence, or be influenced by, the translational course. Non-invasive prenatal aneuploidy testing that utilizes cell-free fetal DNA (cffDNA) circulating in maternal blood is one example of an innovative technology that promises significant benefits for its intended end users; however, it is currently uncertain whether it w...

  8. Mechanisms involved in the induction of aneuploidy: the significance of chromosome loss

    OpenAIRE

    A.I. Seoane; Güerci, A.M; F.N. Dulout

    2000-01-01

    The induction of aneuploidy by physical and chemical agents using different test systems was evaluated. The effect of X-rays, caffeine, acetaldehyde, ethanol, diethylstilbestrol, propionaldehyde, and chloral hydrate was studied by chromosome counting in Chinese hamster embryonic diploid cells. Aneugenic ability of cadmium chloride, cadmium sulfate, potassium dichromate, chromium chloride, nickel chloride, and nickel sulfate was assessed by means of anaphase-telophase analysis in Chinese hamst...

  9. Partial trisomy 2q due to a maternal balanced translocation t(2;22) (q31;p12)

    Energy Technology Data Exchange (ETDEWEB)

    Steinberg, L.S.; Bleiman, M.; Punnett, H.H. [St. Christopher`s Hospital for Children, Philadelphia, PA (United States)] [and others

    1994-09-01

    Features consistent among reported patients with 2q duplications due to familial translocations or de novo duplications include pre- and postnatal growth failure, ocular defects such as congenital glaucoma, cardiac defects, micrognathia, urogenital defects, renal defects, connective tissue laxity, neurologic defects, and dermatologic abnormalities. Genotype/phenotype correlations of patients with trisomy 2q due to familial translocations are complicated by the presence of the deletions of the other chromosome involved. We have had the opportunity to observe `pure` trisomy 2q31-qter resulting from adjacent-1 segregation from 46,XX,t(2;22)(q31;p12) in a carrier mother with apparent loss of the 22 NOR region. He was the 2453 gm product of a gestation complicated by gestational diabetes to a 29-year-old G1 P0 mother and a 30-year-old father. At birth, he was noted to have hypotonia, micrognathia, microphthalmia, left cryptorchidism, hypospadias, bilateral clinodactyly of the fifth digits, mild hyperextensibility of the joints, dry skin disorder, and bilateral hydronephrosis by ultrasound. He was treated for hypoglycemia in the nursery and had a vesicostomy at two months for vesicoureteral reflux. A hearing test at two months found moderate hearing loss in the right ear and mild to moderate hearing loss in the left ear. At 3 months he had surgery for a PDA and bilateral glaucoma and was treated for periods of hypothermia and type IV renal tubular acidosis. This patient and others with unbalanced translocations involving the NOR region of an acrocentric chromosome allow for genotype/phenotype correlation of the `pure` trisomic region.

  10. Multiple marker screening test: identification of fetal cystic hygroma, hydrops, and sex chromosome aneuploidy.

    Science.gov (United States)

    Wenstrom, K D; Boots, L R; Cosper, P C

    1996-01-01

    The goal of this study was to determine if the multiple marker screening test (maternal serum alpha-fetoprotein, unconjugated estriol, human chorionic gonadotrophin, and maternal age) detects fetal Turner syndrome or just cystic hygroma/hydrops. Multiple marker screening tests from 4 groups were compared: 1) Turner syndrome with hydrops/ hygroma group (n = 10) = fetuses with cystic hygroma/hydrops and a 45X karyotype, 2) Turner syndrome without hydrops/hygroma (n = 9) = sonographically unremarkable fetal Turner syndrome or Turner mosaic, 3) hydrops group (n = 8) = all cases of fetal cystic hygroma/hydrops excluding Turner syndrome, 4) sex chromosome aneuploidy group (n = 16) = other sonographically normal fetal sex chromosome aneuploidies. Positive screening tests (Down syndrome risk > or = 1:190 or MSAFP > or = 2.5 MOM) were found in 60% (6/10) of the Turner syndrome with hydrops/hygroma group, but only 11% (1/9) of the Turner syndrome without hydrops/hygroma group (P = .04). The incidence of positive screening tests in the Hydrops group was 75% (6/8), while it was only 12.5% (2/16) in the other sex chromosome aneuploidy group. We conclude that the multiple marker screening test identifies fetuses with cystic hygroma/hydrops, and may do so independently of the etiology of the hydrops. PMID:8796763

  11. Effects of cadmium on aneuploidy and hemocyte parameters in the Pacific oyster, Crassostrea gigas

    International Nuclear Information System (INIS)

    Pacific oysters, Crassostrea gigas, are commonly reared in estuaries where they are exposed to anthropogenic pollution. Much research has been made on the toxicity of cadmium to aquatic organisms because the compound recurrently contaminates their environment. Our study examined the influence of cadmium on aneuploidy level (lowered chromosome number in a percentage of somatic cells) and hemocyte parameters in C. gigas at different stages of life. Adults and juveniles were exposed to two different concentrations of cadmium. The first concentration applied was equivalent to a peak value found in Marennes-Oleron bay (Charente-Maritime, France; 50 ng L-1) and the second was 10 times higher (500 ng L-1). Exposure to 50 ng L-1 cadmium caused a significant decrease in the survival time of C. gigas, but exposure to 500 ng L-1 surprisingly affected the survival time positively. Significant differences in aneuploidy level were observed between the cadmium treatments and the control in adults but not in juveniles or the offspring of the adult groups. The effects of cadmium on hemocyte parameters were analyzed by flow cytometry. Several hemocyte parameters increased significantly after 21 days of cadmium exposure and subsequently decreased. Phenoloxidase-like activity, evaluated by spectrophotometry, varied over the time of the experiment and increased after 66 days of contact with 500 ng L-1 cadmium. Taken together, cadmium at environmentally relevant concentrations seems to have only moderate effects on aneuploidy and hemocyte parameters

  12. Effects of cadmium on aneuploidy and hemocyte parameters in the Pacific oyster, Crassostrea gigas

    Energy Technology Data Exchange (ETDEWEB)

    Bouilly, Karine [IFREMER, Laboratoire de Genetique et Pathologie, La Tremblade 17390 (France); Gagnaire, Beatrice [IFREMER, Laboratoire de Genetique et Pathologie, La Tremblade 17390 (France); Bonnard, Marc [IFREMER, Laboratoire de Genetique et Pathologie, La Tremblade 17390 (France); Thomas-Guyon, Helene [Laboratoire de Biologie et Environnement Marins, FRE-CNRS, 2727, Universite de La Rochelle, 22 Avenue Michel Crepeau, La Rochelle 17042 (France); Renault, Tristan [IFREMER, Laboratoire de Genetique et Pathologie, La Tremblade 17390 (France); Miramand, Pierre [Laboratoire de Biologie et Environnement Marins, FRE-CNRS, 2727, Universite de La Rochelle, 22 Avenue Michel Crepeau, La Rochelle 17042 (France); Lapegue, Sylvie [IFREMER, Laboratoire de Genetique et Pathologie, La Tremblade 17390 (France)]. E-mail: slapegue@ifremer.fr

    2006-06-15

    Pacific oysters, Crassostrea gigas, are commonly reared in estuaries where they are exposed to anthropogenic pollution. Much research has been made on the toxicity of cadmium to aquatic organisms because the compound recurrently contaminates their environment. Our study examined the influence of cadmium on aneuploidy level (lowered chromosome number in a percentage of somatic cells) and hemocyte parameters in C. gigas at different stages of life. Adults and juveniles were exposed to two different concentrations of cadmium. The first concentration applied was equivalent to a peak value found in Marennes-Oleron bay (Charente-Maritime, France; 50 ng L{sup -1}) and the second was 10 times higher (500 ng L{sup -1}). Exposure to 50 ng L{sup -1} cadmium caused a significant decrease in the survival time of C. gigas, but exposure to 500 ng L{sup -1} surprisingly affected the survival time positively. Significant differences in aneuploidy level were observed between the cadmium treatments and the control in adults but not in juveniles or the offspring of the adult groups. The effects of cadmium on hemocyte parameters were analyzed by flow cytometry. Several hemocyte parameters increased significantly after 21 days of cadmium exposure and subsequently decreased. Phenoloxidase-like activity, evaluated by spectrophotometry, varied over the time of the experiment and increased after 66 days of contact with 500 ng L{sup -1} cadmium. Taken together, cadmium at environmentally relevant concentrations seems to have only moderate effects on aneuploidy and hemocyte parameters.

  13. Cytogenetic and molecular genetics and phenotype analysis of a patient with partial trisomy 12p%12P部分三体的细胞-分子遗传学及表型定位研究

    Institute of Scientific and Technical Information of China (English)

    张亚男; 曾艳红; 宋新明; 梁秀龄; 陈争

    2011-01-01

    Objective The aim of this research is to narrow down the genetic abnormalities of the trisomy 12p syndrome in order to identify the candidate gene of the disease. Methods a 13-month old boy with mental retardation and the characteristic facial appearance of patients with the trisomy 12p syndrome was examined. To address whether the child possessed three copies of 12p or a portion of 12p region, we determined the patients karyotype using cytogenetics methodologies, including the conventional G-banding, high resolution banding, and fluorescence in situ hybridization (FISH) methods. The patient's parents' karyotypes were also examined. Results The infant's partial trisomy 12p was originated from his mother's balanced translocation. These defects in eyelid development might be resulted from de novo chromosome abnormalities with the insertion sites of a trisomy fragment (repeating fragment) being at either 12pl3.2 or 13.1 , as these patients' parents all display normal karyotype. Because patients with complete trisomy 12p or their chromosome breaking points of trisomy 12p that lie outside the 12pl3 region did not show small eyelid or without eyelid. Taken together, it was tempting to conclude that these defects in eyelid development might not be caused by changes in gene doses, but rather resulted from breaking points occurred at the 12pl3 region. These breaking points might affect the expression of critical genes that play essential roles during eyelid development. Conclusions The phenotype of trisomy 12p may be associated with express and function of gene at special chromosome region. Further examination of the existence of critical candidate genes whose abnormalities cause trisomy 12p syndrome will need to precisely map the break and insert sites involved in trisomy 12p.%目的 进一步探讨12p部分三体综合征遗传物质增加与临床表现之间的关系.方法 我们对1例具有发育缓慢、精神发育迟滞和面部畸形的13个月大患儿和双亲

  14. Prenatal diagnosis of trisomy 13 on fetal cells obtained from maternal blood after minor enrichment

    NARCIS (Netherlands)

    Oosterwijk, JC; Mesker, WE; Ouwerkerk-Van Velzen, MCM; Knepfle, CFHM; Wiesmeijer, KC; Beverstock, GC; Van Ommen, GJB; Tanke, HJ; Kanhai, HHH

    1998-01-01

    In a pilot study to establish fetal nucleated red blood cell (NRBC) detection in maternal blood, trisomy 13 was diagnosed by FISH analysis at 11 weeks' gestation. The NRBCs were detected after a single-step ficoll density gradient enrichment. In blood samples taken both before and after CVS, 52 and

  15. Twenty-year trends in the prevalence of Down syndrome and other trisomies in Europe

    DEFF Research Database (Denmark)

    Loane, Maria; Morris, Joan K; Addor, Marie-Claude;

    2013-01-01

    This study examines trends and geographical differences in total and live birth prevalence of trisomies 21, 18 and 13 with regard to increasing maternal age and prenatal diagnosis in Europe. Twenty-one population-based EUROCAT registries covering 6.1 million births between 1990 and 2009 participa...

  16. Facial profile markers in second- and third-trimester fetuses with trisomy 18

    NARCIS (Netherlands)

    Vos, F. I.; de Jong-Pleij, E. A. P.; Bakker, Merel; Tromp, E.; Manten, G. T. R.; Bilardo, C. M.

    2015-01-01

    Objectives To evaluate nasal bone length (NBL), maxilla-nasion-mandible (MNM) angle, fetal profile (FP) line, prenasal thickness (PT), prenasal thickness to nasal bone length (PT: NBL) ratio and prefrontal space ratio (PFSR) as markers of trisomy 18 in the second and third trimesters of pregnancy. M

  17. The development of colon innervation in trisomy mice and Hirschsprungs disease

    Institute of Scientific and Technical Information of China (English)

    Ji Cheng Li; Kai Hong Mi; Ji Lin Zhou; LC Busch; W KuhnelC

    2001-01-01

    AIM To study the colon innervation of trisomy16 mouse, an animal model for Downssyndrome, and the expression of protein geneproduct 9.5 ( PGP 9.5) in the stenosed segmentof colon in Hirschsprungs disease (HD).METHODS Trisomy 16 mouse breeding;cytogenetic analysis of trisomy 16 mice; andPGP 9.5 immunohistochemistry of colons oftrisomy 16 mice and HD were carried out.RESULTS Compared with their normalIittermates, the nervous system of colon intrisomy 16 mice was abnormally developed.There existed developmental delay of muscularplexuses of colon, no submucosal plexus wasfound in the colon, and there was 5mmaganglionic bowel aparting from the anus intrisomy 16 mice. The mesentery nerve fiberswere as well developed as shown in their normallittermates. Abundant proliferation of PGP 9.5positive nerve fibers was revealed in thestenosed segment of HD colon.CONCLUSION Trisomy 16 mice could serve asaganglionic bowel in the distal part of colon.Abundant proliferation of PGP 9.5 positive fibersresulted from extrinsic nerve compensation,since no ganglionic cells were observed in thestenosed segment of the colon in HD. HD has agenetic tendency.

  18. Unexplained False Negative Results in Noninvasive Prenatal Testing: Two Cases Involving Trisomies 13 and 18

    Directory of Open Access Journals (Sweden)

    R. Hochstenbach

    2015-01-01

    Full Text Available Noninvasive prenatal testing (NIPT validation studies show high sensitivity and specificity for detection of trisomies 13, 18, and 21. False negative cases have rarely been reported. We describe a false negative case of trisomy 13 and another of trisomy 18 in which NIPT was commercially marketed directly to the clinician. Both cases came to our attention because a fetal anatomy scan at 20 weeks of gestation revealed multiple anomalies. Karyotyping of cultured amniocytes showed nonmosaic trisomies 13 and 18, respectively. Cytogenetic investigation of cytotrophoblast cells from multiple placental biopsies showed a low proportion of nontrisomic cells in each case, but this was considered too small for explaining the false negative NIPT result. The discordant results also could not be explained by early gestational age, elevated maternal weight, a vanishing twin, or suboptimal storage or transport of samples. The root cause of the discrepancies could, therefore, not be identified. The couples involved experienced difficulties in accepting the unexpected and late-adverse outcome of their pregnancy. We recommend that all parties involved in caring for couples who choose NIPT should collaborate to clarify false negative results in order to unravel possible biological causes and to improve the process of patient care from initial counseling to communication of the result.

  19. On the paternal origin of trisomy 21 Down syndrome

    Directory of Open Access Journals (Sweden)

    Jonsson Anna

    2010-02-01

    Full Text Available Abstract Background Down syndrome (DS, characterized by an extra free chromosome 21 is the most common genetic cause for congenital malformations and learning disability. It is well known that the extra chromosome 21 originates from the mother in more than 90% of cases, the incidence increases with maternal age and there is a high recurrence in young women. In a previous report we have presented data to indicate that maternal trisomy 21 (T21 ovarian mosaicism might provide the major causative factor underlying these patterns of DS inheritance. One important outstanding question concerns the reason why the extra chromosome 21 in DS rarely originates from the father, i.e. in less than 10% of T21 DS cases. We here report data indicating that one reason for this parental sex difference is a very much lower degree of fetal testicular in comparison to ovarian T21 mosaicism. Results We used fluorescence in situ hybridisation (FISH with two chromosome 21-specific probes to determine the copy number of chromosome 21 in fetal testicular cell nuclei from four male fetuses, following termination of pregnancy for a non-medical/social reason at gestational age 14-19 weeks. The cells studied were selected on the basis of their morphology alone, pending immunological specification of the relevant cell types. We could not detect any indication of testicular T21 mosaicism in any of these four male fetuses, when analysing at least 2000 cells per case (range 2038-3971, total 11.842. This result is highly statistically significant (p Conclusion Based on these observations we suggest that there is a significant sex difference in degrees of fetal germ line T21 mosaicism. Thus, it would appear that most female fetuses are T21 ovarian mosaics, while in sharp contrast most male fetuses may be either very low grade T21 testicular mosaics or they may be non-mosaics. We further propose that this sex difference in germ line T21 mosaicism may explain the much less frequent

  20. Counseling parents before prenatal diagnosis: do we need to say more about the sex chromosome aneuploidies?

    Science.gov (United States)

    Lalatta, Faustina; Tint, G Stephen

    2013-11-01

    Sex chromosome trisomies (SCT), an extra X chromosome in females (triple X, XXX), males with an extra X chromosome (Klinefelter syndrome, XXY) or an extra Y chromosome (XYY) occur because of errors during meiosis and are relatively frequent in humans. Their identification has never been the goal of prenatal diagnosis (PD) but they almost never escape detection by any of the methods commonly in use. Despite recommendations and guide-lines which emphasize the importance of structured counseling before and after PD, most women remain unaware that testing for serious genetic abnormalities is more likely to uncover these trisomies. With the increasing use of PD more and more prospective parents receive a diagnosis of sex chromosome trisomies and are faced with the dilemma of whether to terminate the pregnancy or to carry it to term. Despite the dramatic and emotionally devastating consequences of having to make such a decision, they have little opportunity to consider in advance the possible outcomes of such a pregnancy and, rather than relying on their own feelings and judgements, are forced to depend on the advice of counseling professionals who may or may not themselves be fully aware of what having an extra sex chromosome can mean to the development of a child. We address here the principles of reproductive autonomy together with an analysis of the major issues that ought to be discussed with the parents before a PD is carried out in order to minimize detrimental effects caused by this unexpected finding.

  1. Mosaicism for a chromosome 8-derived minute marker chromosome in a patient with manifestations of trisomy 8 mosaicism

    Energy Technology Data Exchange (ETDEWEB)

    Spinner, N.B.; Grace, K.R.; Owens, N.L. [Children`s Hospital of Philadelphia, PA (United States)] [and others

    1995-03-13

    We describe a patient with manifestations of the mosaic trisomy 8 syndrome and mosaicism for a minute marker chromosome. Fluorescence in situ hybridization (FISH) with a chromosome 8 probe confirmed that the marker was derived from chromosome 8. This is the smallest piece of chromosome 8 to be reported in a patient with mosaic trisomy 8 syndrome. When the clinical picture is strongly suggestive of trisomy for a specific chromosome region, we believe that FISH can be used to test markers in a guided, rather than random, fashion. 8 refs., 3 figs.

  2. Application of primed in situ labeling technique in diagnosis of human chromosomal aneuploidy chimera%引物原位标记技术在人类染色体非整倍体嵌合体诊断中的应用

    Institute of Scientific and Technical Information of China (English)

    黄元河; 冯治; 潘乔丹

    2013-01-01

    Objective: To explore a new rapid and specific method for diagnosis of human chromosomal aneuploidy chimera. Methods: Primed in situ labeling technique and chromosomal G band technique were used to detect chimera of two cases with triso-my 21 and three cases with Turn syndrome, then the results were compared. Results: During interphase and nuclear fission during meta-phase, primed in situ labeling technique detected 21 and X chromosomes specifically, the labeling rates were 90% and 89% , respectively. The number of cells with abnormal karyotypes among 100 cells of trisomy 21 and Turn syndrome detected by primed in situ labeling technique was higher than that detected by chromosomal G band. Conclusion: Primed in situ labeling technique can rapidly and accurately detect chromosomal numerical abnormality, combined with chromosomal G band, which can improve the accuracy of diagnosis of human chromosomal aneuploidy chimera.%目的:探讨快速和准确诊断人类染色体非整倍体嵌合体的新方法.方法:采用引物原位标记(PRINS)技术和染色体G显带技术检测2例21三体嵌合体和3例Turn综合征嵌合体,并比较其结果.结果:在间期核和中期分裂相中,PRINS技术均能特异性地检测出21号和X染色体,其标记率分别为90%和89%;PRINS技术检测的21三体嵌合体和Turn综合征嵌合体100个细胞中,异常核型细胞数目高于染色体G显带技术检测.结论:PRINS技术能够快速、准确地检测染色体数目异常,与染色体G显带技术相结合,可提高人类染色体非整倍体嵌合体诊断的准确性.

  3. Tracking subtle stereotypes of children with trisomy 21: from facial-feature-based to implicit stereotyping.

    Directory of Open Access Journals (Sweden)

    Claire Enea-Drapeau

    Full Text Available BACKGROUND: Stigmatization is one of the greatest obstacles to the successful integration of people with Trisomy 21 (T21 or Down syndrome, the most frequent genetic disorder associated with intellectual disability. Research on attitudes and stereotypes toward these people still focuses on explicit measures subjected to social-desirability biases, and neglects how variability in facial stigmata influences attitudes and stereotyping. METHODOLOGY/PRINCIPAL FINDINGS: The participants were 165 adults including 55 young adult students, 55 non-student adults, and 55 professional caregivers working with intellectually disabled persons. They were faced with implicit association tests (IAT, a well-known technique whereby response latency is used to capture the relative strength with which some groups of people--here photographed faces of typically developing children and children with T21--are automatically (without conscious awareness associated with positive versus negative attributes in memory. Each participant also rated the same photographed faces (consciously accessible evaluations. We provide the first evidence that the positive bias typically found in explicit judgments of children with T21 is smaller for those whose facial features are highly characteristic of this disorder, compared to their counterparts with less distinctive features and to typically developing children. We also show that this bias can coexist with negative evaluations at the implicit level (with large effect sizes, even among professional caregivers. CONCLUSION: These findings support recent models of feature-based stereotyping, and more importantly show how crucial it is to go beyond explicit evaluations to estimate the true extent of stigmatization of intellectually disabled people.

  4. Prenatal ultrasonic screening of fetuses with trisomy 18%18-三体综合征胎儿的产前超声筛查

    Institute of Scientific and Technical Information of China (English)

    栗河舟; 王铭; 许雅娟; 吴玥丽; 雷冬梅; 刘云; 李洁; 林杉; 孟繁凌

    2012-01-01

    目的:评价18三体综合征胎儿的超声表现特征和产前超声筛查的价值.方法:对羊膜腔穿刺或脐血管穿刺确诊为18-三体综合征的27例胎儿超声声像图进行分析.结果:27例18-三体胎儿均表现为胎儿结构异常,每例胎儿可检出四项及四项以上超声异常,最常见的超声改变是心脏畸形,共25例;其它常见的异常包括重叠指17例,单脐动脉11例,小下颌10例,上消化道梗阻9例,脉络丛囊肿及桡骨发育不良或缺如各8例,草莓头7例,小脑发育不良、小脑延髓池扩大、脐膨出及腕关节异常各6例,宫内生长受限11例,羊水过多19例.结论:超声检查是产前筛查18-三体综合征胎儿的有效手段.%Objective: To evaluate the characteristics of ultrasonic manifestations and value of prenatal ultrasonic screening for fetuses with trisomy 18. Methods: The ultrasonic images of 27 fetuses diagnosed as trisomy 18 definitely by amniocentesis and needle puncture of umbilical blood vessels were analyzed. Results; All the fetuses with trisomy 18 were found with fetal structural abnormality, each fetus was found with four kinds or more than four kinds of ultrasonic abnormalities, the most common ultrasonic abnormalities were cardiac abnormalities, which were found in 25 fetuses; the other common abnormalities included abnormal fingers overlap (17 fetuses) , single umbilical artery (11 fetuses) , micrognathia (10 fetuses) , upper gastrointestinal obstruction (9 fetuses) , choroid plexus cyst ( 8 fetuses) , dysplasia or absence of radius (8 fetuses) , strawberry head (7 fetuses) , cerebellar hypopksia (6 fetuses) , dilatation of cisterna magna (6 fetuses) , omphalocele (6 fetuses) , wrist abnormalities (6 fetuses) , intrauterine growth restriction (11 fetuses) , and polyhydramnios ( 19 fetuses) . Conclusion; Ultrasonographyis an effective method for prenatal screening of fetuses with trisomy 18.

  5. The level of ADAM12-S in maternal serum is an early first-trimester marker of fetal trisomy 18

    DEFF Research Database (Denmark)

    Laigaard, Jennie; Christiansen, Michael; Frohlich, Camilla;

    2005-01-01

    (DS) fetus. On the basis of this finding, it was suggested that ADAM12-S might be a useful maternal serum marker of fetal chromosomal disease. OBJECTIVE: Retrospective examination of the use of ADAM12-S as a marker for fetal trisomy 18. METHOD: Serum samples were obtained from ten women during...... the first semester of their pregnancies with fetuses that had trisomy 18. An ELISA was used to determine the levels of ADAM12 in maternal serum. Results were compared to ADAM12-S levels, previously measured in the serum of 170 women carrying normal pregnancies during the first trimester. RESULTS: In all...... cases, the ADAM12-S concentration in maternal serum samples was lower in trisomy 18 pregnancies than in normal pregnancies, with a median multiple of the median (MoM) of 0.28 (p trisomy 18...

  6. Dosage Effects of X and Y Chromosomes on Language and Social Functioning in Children with Supernumerary Sex Chromosome Aneuploidies: Implications for Idiopathic Language Impairment and Autism Spectrum Disorders

    Science.gov (United States)

    Lee, Nancy Raitano; Wallace, Gregory L.; Adeyemi, Elizabeth I.; Lopez, Katherine C.; Blumenthal, Jonathan D.; Clasen, Liv S.; Giedd, Jay N.

    2012-01-01

    Background: Supernumerary sex chromosome aneuploidies (X/Y-aneuploidies), the presence of extra X and/or Y chromosomes, are associated with heightened rates of language impairments and social difficulties. However, no single study has examined different language domains and social functioning in the same sample of children with tri-, tetra-, and…

  7. Detection of skewed X-chromosome inactivation in Fragile X syndrome and X chromosome aneuploidy using quantitative melt analysis.

    Science.gov (United States)

    Godler, David E; Inaba, Yoshimi; Schwartz, Charles E; Bui, Quang M; Shi, Elva Z; Li, Xin; Herlihy, Amy S; Skinner, Cindy; Hagerman, Randi J; Francis, David; Amor, David J; Metcalfe, Sylvia A; Hopper, John L; Slater, Howard R

    2015-07-01

    Methylation of the fragile X mental retardation 1 (FMR1) exon 1/intron 1 boundary positioned fragile X related epigenetic element 2 (FREE2), reveals skewed X-chromosome inactivation (XCI) in fragile X syndrome full mutation (FM: CGG > 200) females. XCI skewing has been also linked to abnormal X-linked gene expression with the broader clinical impact for sex chromosome aneuploidies (SCAs). In this study, 10 FREE2 CpG sites were targeted using methylation specific quantitative melt analysis (MS-QMA), including 3 sites that could not be analysed with previously used EpiTYPER system. The method was applied for detection of skewed XCI in FM females and in different types of SCA. We tested venous blood and saliva DNA collected from 107 controls (CGG chromosome test; (ii) locus-specific XCI skewing towards the hypomethylated state in FM females; and (iii) skewed XCI towards the hypermethylated state in SCA with 3 or more X chromosomes, and in 5% of the 47,XXY individuals. MS-QMA output also showed significant correlation with the EpiTYPER reference method in FM males and females (P < 0.0001) and SCAs (P < 0.05). In conclusion, we demonstrate use of MS-QMA to quantify skewed XCI in two applications with diagnostic utility.

  8. The fragile Y hypothesis: Y chromosome aneuploidy as a selective pressure in sex chromosome and meiotic mechanism evolution.

    Science.gov (United States)

    Blackmon, Heath; Demuth, Jeffery P

    2015-09-01

    Loss of the Y-chromosome is a common feature of species with chromosomal sex determination. However, our understanding of why some lineages frequently lose Y-chromosomes while others do not is limited. The fragile Y hypothesis proposes that in species with chiasmatic meiosis the rate of Y-chromosome aneuploidy and the size of the recombining region have a negative correlation. The fragile Y hypothesis provides a number of novel insights not possible under traditional models. Specifically, increased rates of Y aneuploidy may impose positive selection for (i) gene movement off the Y; (ii) translocations and fusions which expand the recombining region; and (iii) alternative meiotic segregation mechanisms (achiasmatic or asynaptic). These insights as well as existing evidence for the frequency of Y-chromosome aneuploidy raise doubt about the prospects for long-term retention of the human Y-chromosome despite recent evidence for stable gene content in older non-recombining regions.

  9. Short exposure to paclitaxel induces multipolar spindle formation and aneuploidy through promotion of acentrosomal pole assembly

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Paclitaxel is a widely used microtubule drug and cancer medicine. Here we report that by short exposure to paclitaxel at a low dose, multipolar spindles were induced in mitotic cells without centrosome amplification. Both TPX2 depletion and Aurora-A overexpression antagonized the multipolarity. Live cell imaging showed that some paclitaxel-treated cells accomplished multipolar cell division and a portion of the daughter cells went on to the next round of mitosis. The surviving cells grew into clones with varied genome content. The results indicated that an aneuploidy population could be induced by short exposure to paclitaxel at a low dose, implicating potential side effects of paclitaxel.

  10. Molecular cytogenetic determination of a deletion/duplication of 1q that results in a trisomy 18 syndrome-like phenotype

    Energy Technology Data Exchange (ETDEWEB)

    Mewar, R.; Harrison, W.; Weaver, D.D.; Palmer, C.; Davee, M.A.; Overhauser, J.

    1994-08-15

    We report on an infant who presented at birth with some characteristics of trisomy 18 syndrome, including low birth weight, facial abnormalities, overlapping fingers, and congenital heart defects. On chromosome analysis, no additional chromosome 18 was observed and both chromosome 18 homologues appeared normal. However, a small piece of chromosomal material of unknown origin was detected at the tip of the long arm of chromosome 1. Fluorescence in situ hybridization (FISH) using whole chromosome 18 painting probes disclosed no additional hybridization at the telomere of 1q, suggesting that the material was derived from another chromosome. Further chromosome painting experiments suggested that the telomeric addition was of chromosome 1 origin. To identify subchromosomal regions involved in the rearrangement, additional FISH analyses were performed using single copy and repetitive DNA probes mapping different portions of chromosome 1. The analyses showed that probes mapping to 1q34-43 were duplicated in the derivative chromosome 1. In addition, a DNA probe mapping to 1q44 was found to be deleted from the derivative chromosome 1. Our composite analysis suggests that a deletion and a duplication of chromosome 1q can result in some of the clinical findings usually associated with trisomy 16 syndrome. These results demonstrate the usefulness of FISH analysis when karyotype analysis is not consistent with the clinical description. 23 refs., 3 figs., 2 tabs.

  11. Cell-Free Fetal DNA and Cell-Free Total DNA Levels in Spontaneous Abortion with Fetal Chromosomal Aneuploidy

    OpenAIRE

    Ji Hyae Lim; Min Hyoung Kim; You Jung Han; Da Eun Lee; So Yeon Park; Jung Yeol Han; Moon Young Kim; Hyun Mee Ryu

    2013-01-01

    BACKGROUND: Cell-free fetal DNA and cell-free total DNA in maternal circulation have been proposed as potential markers for noninvasive monitoring of the placental condition during the pregnancy. However, the correlation of and change in cell-free fetal DNA and cell-free total DNA in spontaneous abortion (SA) with fetal chromosomal aneuploidy have not yet been reported. Therefore, we investigated cell-free fetal DNA and cell-free total DNA levels in SA women with fetal chromosomal aneuploidy....

  12. A validated FISH trisomy index demonstrates the hyperdiploid and nonhyperdiploid dichotomy in MGUS

    OpenAIRE

    Chng, Wee Joo; Wier, Scott A. Van; Ahmann, Gregory J.; Winkler, Jerry M.; Jalal, Syed M.; Bergsagel, Peter Leif; Chesi, Marta; Trendle, Mike C.; Oken, Martin M.; Blood, Emily; Henderson, Kim; Santana-Dávila, Rafael; Kyle, Robert A.; Gertz, Morie A; Lacy, Martha Q.

    2005-01-01

    Two major genetic categories of multiple myeloma (MM) exist. Hyperdiploid MM (48 to 74 chromosomes, median 53 chromosomes) is associated with trisomies especially of chromosomes 3, 7, 9, 11, 15, and 19, whereas the nonhyperdiploid (< 48 chromosomes or more than 74 chromosomes) MM is associated with primary translocations such as t(11;14), t(4;14), and t(14;16). Whether this dichotomy exists in monoclonal gammopathy of undetermined significance (MGUS) is uncertain due to limitations of current...

  13. Trisomy 8, a Cytogenetic Abnormality in Myelodysplastic Syndromes, Is Constitutional or Not?

    Directory of Open Access Journals (Sweden)

    Sílvia Saumell

    Full Text Available Isolated trisomy 8 is not considered presumptive evidence of myelodysplastic syndrome (MDS in cases without minimal morphological criteria. One reason given is that trisomy 8 (+8 can be found as a constitutional mosaicism (cT8M. We tried to clarify the incidence of cT8M in myeloid neoplasms, specifically in MDS, and the diagnostic value of isolated +8 in MDS. Twenty-two MDS and 10 other myeloid neoplasms carrying +8 were studied. Trisomy 8 was determined in peripheral blood by conventional cytogenetics (CC and on granulocytes, CD3+ lymphocytes and oral mucosa cells by fluorescence in situ hybridization (FISH. In peripheral blood CC, +8 was seen in 4/32 patients. By FISH, only one patient with chronic myelomonocytic leukemia showed +8 in all cell samples and was interpreted as a cT8M. In our series +8 was acquired in all MDS. Probably, once discarded cT8M by FISH from CD3+ lymphocytes and non-hematological cells, +8 should be considered with enough evidence to MDS.

  14. Trisomy 12 in chronic lymphocytic leukemia and hairy cell leukemia: a cytogenetic and interphase cytogenetic study.

    Science.gov (United States)

    Cuneo, A; Bigoni, R; Balboni, M; Carli, M G; Piva, N; Fagioli, F; Latorraca, A; Wlodarska, I; van den Berghe, H; Castoldi, G

    1994-09-01

    Fluorescent in situ hybridization (FISH) with a chromosome 12-specific pericentromeric probe was performed in 42 patients with B-cell chronic lymphocytic leukemia (CLL) and in 10 patients with hairy cell leukemia (HCL). In all cases, a normal karyotype in more than 10 metaphase cells was obtained by conventional chromosome study. FISH documented that 6/42 patients with CLL in fact had trisomy 12 in 15-49% interphase cells. Sequential FISH studies were performed in 2 cases, showing an increase of percentage of trisomic cells over a 2-month to 4-year period. Two out of 10 patients with HCL, one of whom had morphologic features consistent with a diagnosis of HCL variant, showed 5.5 and 10% interphase nuclei with three fluorescent signals, a finding suggestive of the presence of trisomy 12. Combined immunophenotyping and FISH staining in these patients with HCL documented that trisomic cells were CD11c-positive, CD13-negative, and CD2-negative. We conclude that FISH is a sensitive technique allowing for the detection of trisomy 12 in a fraction of cytogenetically normal patients affected with CLL and HCL. PMID:7858495

  15. [Confirmation of a prenatal diagnosis of trisomy 13 with comparative genomic hybridization (CGH)].

    Science.gov (United States)

    Marton, T; Thein, A; Bán, Z; Soothill, P; Oroszné, N J; Papp, Z

    2001-05-13

    Trisomy 13 was diagnosed with genetic amniocentesis in a fetus of a 50 years old patient. Fetopathologic examination has shown cyclopy, proboscis and semilobar holoprosencephaly of the fetus, which is consistent with Patau syndrome. DNA was extracted from frozen liver tissue. Result of comparative genomic hybridization (CGH) was consistent with trisomy 13. They processed the DNA according Kallioniemi's method with modifications. CGH was developed for cancer genetics in mid 90s and now it is widely used in prenatal diagnosis too. CGH allows global analysis to detect unbalanced chromosome gains and losses in the whole genome in a single experiment without the need for cell culture. Significant results can be expected in those cases where conventional cytogenetics is not able to provide an answer either because postmortem tissue is not appropriate for cytogenetics or because the chromosomal change is sub-microscopical. CGH is a fluorescent in situ hybridization on a healthy target metaphase, with equal amount of competitive hybridization of green labelled digested test DNA and red labelled digested control DNA. Red to green ratio is assessed with the help of an image analyser. Green dominance represents chromosome gain, while red shift chromosome loss. In the paper they present the fetopathologic report of a trisomy 13 fetus and illustrate the method being the first Hungarian obstetric case diagnosed by CGH. PMID:11419300

  16. Trisomy 9 syndrome: Report of a case with Crohn disease and review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Wolldridge, J.; Zuncih, J. [Indiana University School of Medicine, Gary, IN (United States)

    1995-04-10

    We report on a 6-year-old boy with mosaic trisomy 9. The patient was born at 42 weeks of gestation to a 27-year-old G1 white woman. Birth weight was 2,820 g, length 52 cm, and Apgar scores were 4 and 6 at 1 and 5 min, respectively. The infant presented with apparently low-set ears, overfolded helices, epicanthal folds, prominent nasal bridge, high-arched palate, micrognathia, bilateral dislocated hips, left genu recurvatum, and cryptorchidism. Chromosome analysis showed an unusual karyotype: 47,XY,+inv(9qh+)/47,XY,+mar. The marker chromosome was thought to be a remnant of the inv (9qh+), while the father`s was 46,XY. At age 5 months, the patient developed seizures and gastroesophageal reflux. Crohn disease was diagnosed at age 2 years, although symptoms began at age 1 year. Recurrent bouts of pneumonia have occurred since the patient`s birth. Severe psychomotor retardation was also noted. Trisomy 9 syndrome was first reported in 1973. Over 30 cases have been reported since then. Of these case reports, only 5 patients were older than 1 year. Inflammatory bowel disease has been reported in association with other chromosome abnormalities, but to our knowledge, has not been reported in trisomy 9 syndrome. 39 refs., 4 figs., 2 tabs.

  17. Early Biochemical Screening for Fetal Aneuploidy in the First Trimester

    DEFF Research Database (Denmark)

    Tørring, Niels

    2013-01-01

    validation of the Roche Elecsys® free βhCG and PAPP-A assays were performed, including method comparisons with the Brahms Kryptor, AutoDELFIA PerkinElmer and Siemens Immulite assays. Furthermore a clinical validation including genertion of assay specific medians for PAPP-A and free βhCG from gestational age...... 8+0 to 14+0 weeks, and clinical test performance of risk assesment was conducted. Results The in-between day imprecision of the Elecsys® free βhCG and PAPP-A assays were between 1.0 and 2.8%. Comparison (Passing/Bablok regression) of free βhCG and PAPP-A from Roche Elecsys® and the Brahms Kryptor...

  18. Non-invasive prenatal testing for aneuploidy and beyond

    DEFF Research Database (Denmark)

    Dondorp, Wybo; de Wert, Guido; Bombard, Yvonne;

    2015-01-01

    the potential of helping the practice better achieve its aim of facilitating autonomous reproductive choices, provided that balanced pretest information and non-directive counseling are available as part of the screening offer. Depending on the health-care setting, different scenarios for NIPT-based screening...... the responsible innovation of prenatal screening on the basis of ethical principles. Crucial elements are the quality of the screening process as a whole (including non-laboratory aspects such as information and counseling), education of professionals, systematic evaluation of all aspects of prenatal screening...

  19. Human germ cell formation in xenotransplants of induced pluripotent stem cells carrying X chromosome aneuploidies.

    Science.gov (United States)

    Dominguez, Antonia A; Chiang, H Rosaria; Sukhwani, Meena; Orwig, Kyle E; Reijo Pera, Renee A

    2014-09-22

    Turner syndrome is caused by complete or partial loss of the second sex chromosome and is characterized by spontaneous fetal loss in >90% of conceptions. Survivors possess an array of somatic and germline clinical characteristics. Induced pluripotent stem cells (iPSCs) offer an opportunity for insight into genetic requirements of the X chromosome linked to Turner syndrome. We derived iPSCs from Turner syndrome and control individuals and examined germ cell development as a function of X chromosome composition. We demonstrate that two X chromosomes are not necessary for reprogramming or maintenance of pluripotency and that there are minimal differences in gene expression, at the single cell level, linked to X chromosome aneuploidies. Formation of germ cells, as assessed in vivo through a murine xenotransplantation model, indicated that undifferentiated iPSCs, independent of X chromosome composition, are capable of forming germ-cell-like cells (GCLCs) in vivo. In combination with clinical data regarding infertility in women with X chromosome aneuploidies, results suggest that two intact X chromosomes are not required for human germ cell formation, qualitatively or quantitatively, but rather are likely to be required for maintenance of human germ cells to adulthood.

  20. Prenatal detection of aneuploidy and imbalanced chromosomal arrangements by massively parallel sequencing.

    Directory of Open Access Journals (Sweden)

    Shan Dan

    Full Text Available Fetal chromosomal abnormalities are the most common reasons for invasive prenatal testing. Currently, G-band karyotyping and several molecular genetic methods have been established for diagnosis of chromosomal abnormalities. Although these testing methods are highly reliable, the major limitation remains restricted resolutions or can only achieve limited coverage on the human genome at one time. The massively parallel sequencing (MPS technologies which can reach single base pair resolution allows detection of genome-wide intragenic deletions and duplication challenging karyotyping and microarrays as the tool for prenatal diagnosis. Here we reported a novel and robust MPS-based method to detect aneuploidy and imbalanced chromosomal arrangements in amniotic fluid (AF samples. We sequenced 62 AF samples on Illumina GAIIx platform and with averagely 0.01× whole genome sequencing data we detected 13 samples with numerical chromosomal abnormalities by z-test. With up to 2× whole genome sequencing data we were able to detect microdeletion/microduplication (ranged from 1.4 Mb to 37.3 Mb of 5 samples from chorionic villus sampling (CVS using SeqSeq algorithm. Our work demonstrated MPS is a robust and accurate approach to detect aneuploidy and imbalanced chromosomal arrangements in prenatal samples.

  1. Analysis of micronuclei and microtubule arrangement to identify aneuploidy-inducing agents in cultured mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Degrassi, F.; Pisano, C. [Centre di Genetica Evoluzionistica, Rome (Italy); Tanzarella, C.; Antoccia, A.; Battistoni, A. [Universita La Sapienza, Rome (Italy)

    1993-12-31

    The development of in vitro test methods to detect environmental agents that might induce aneuploidy is of crucial importance in genotoxicity testing. Chromosome numerical changes may arise from damage to various cell structures and activities such as spindle components or kinetochore proteins as well as from damage to the chromosomes. Therefore, the development of effective assays to identify chromosome misdistribution in mammalian cell cultures requires the contribution of different research areas such as cytogenetics, molecular biology and cell biology. Recently, we have been working at the development of an in vitro test for aneuploidy-inducing agents combining the micronucleus assay with the immunofluorescent staining of kinetochores in micronuclei (MN). The assay has been standardized by analyzing the induction of MN containing kinetochores (CREST-positive MN) after a number of agents with different mechanism of action. Subsequently, the optimization of the assay has been carried out by introducing cytochalasin-B (cyt-B) in the test protocol in order to score MN in cells that have undergone one cell cycle. Finally, with the aim of providing an understanding of the mechanisms responsible for the production of CREST-positive MN we have analyzed the cellular structures involved in mitotic division by using specific antibodies in immunofluorescence studies.

  2. Constitutive aneuploidy and genomic instability in the single-celled eukaryote Giardia intestinalis.

    Science.gov (United States)

    Tůmová, Pavla; Uzlíková, Magdalena; Jurczyk, Tomáš; Nohýnková, Eva

    2016-08-01

    Giardia intestinalis is an important single-celled human pathogen. Interestingly, this organism has two equal-sized transcriptionally active nuclei, each considered diploid. By evaluating condensed chromosome numbers and visualizing homologous chromosomes by fluorescent in situ hybridization, we determined that the Giardia cells are constitutively aneuploid. We observed karyotype inter-and intra-population heterogeneity in eight cell lines from two clinical isolates, suggesting constant karyotype evolution during in vitro cultivation. High levels of chromosomal instability and frequent mitotic missegregations observed in four cell lines correlated with a proliferative disadvantage and growth retardation. Other cell lines, although derived from the same clinical isolate, revealed a stable yet aneuploid karyotype. We suggest that both chromatid missegregations and structural rearrangements contribute to shaping the Giardia genome, leading to whole-chromosome aneuploidy, unequal gene distribution, and a genomic divergence of the two nuclei within one cell. Aneuploidy in Giardia is further propagated without p53-mediated cell cycle arrest and might have been a key mechanism in generating the genetic diversity of this human pathogen. PMID:27004936

  3. Telomere shortening correlates with increasing aneuploidy of chromosome 8 in human hepatocellular carcinoma.

    Science.gov (United States)

    Plentz, Ruben R; Schlegelberger, Brigitte; Flemming, Peer; Gebel, Michael; Kreipe, Hans; Manns, Michael P; Rudolph, K Lenhard; Wilkens, Ludwig

    2005-09-01

    Chromosomal instability (CIN) leads to an increase in aneuploidy and chromosomal aberrations in human hepatocellular carcinoma (HCC). Telomere shortening appears as one mechanism fostering the development of CIN. Whether telomere shortening correlates to specific genetic changes that characterize a certain type of cancer has yet to be established. In our recent study, we combined on a cellular level the analysis of hepatocellular telomere fluorescent intensity (TFI) and copy number of chromosome 8-one of the hallmark chromosomal alterations in hepatocellular carcinoma (HCC). We investigated 15 cytological fine-needle biopsies of aneuploid HCC and 5 touch prints of cadaver livers without cancer. Hepatocyte-specific TFI and the measurement of centromere-specific probe for chromosome 8 were both performed by quantitative fluorescence in situ hybridization (qFISH) or FISH. Combined analysis of both methods (coFISH) allowed measurement of telomere length and chromosome 8 copy number on a single cell level. We observed that telomere shortening correlates significantly with increasing copy number of chromosome 8 in HCC on the cellular level. Above the level of 5 copies of chromosome 8 per nucleus, no further shortening of telomeres was found, indicating that telomeres had reached a critically short length at this stage of aneuploidy. In conclusion, our study gives direct evidence that telomere shortening is linked to a specific genetic alteration characteristic for human HCC. PMID:16116624

  4. Intrauterine death in singleton pregnancies with trisomy 21, 18, 13 and monosomy X

    Directory of Open Access Journals (Sweden)

    Vanessa Vigna Goulart

    2016-04-01

    Full Text Available Summary A retrospective study from November 2004 to May 2012, conducted at the Obstetric Clinic of Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HC-FMUSP, which included 92 singleton pregnancies with prenatal diagnosis of trisomy of chromosome 21 (T21, 18, 13 (T13/18 and monosomy X (45X, with diagnosis performed until the 26th week of pregnancy. The aim of the study was to describe the frequency and to investigate predictors of spontaneous fetal death (FD. Diagnosis (T21, n=36; T13/18, n=25; 45X, n=31 was made at a mean gestational age of 18.3±3.7 weeks, through chorionic villus biopsy (n=22,24%, amniocentesis (n=66, 72% and cordocentesis (n=4, 4%. Major malformations were present in 45 (49%; with hydrops in 32 (35% fetuses, more frequently in 45X [n=24/31, 77% vs. T21 (n=6/36, 17% and T13/18 (n=2/25, 8%, p<0.001]. Specialized fetal echocardiography was performed in 60% (55/92. Of these, 60% (33/55 showed changes in heart morphology and/or function. Fetuses with T13/18 had a higher incidence of cardiac anomalies [60 vs. 25% (T21 and 29% (45X, p= 0.01]. FD occurred in 55 (60% gestations, being more frequent in 45X [n=26/31, 84% vs. T21 (n=13/36, 36% and T13/18 (n=16/25, 64%, p<0.01]. Stepwise analysis showed a correlation between hydrops and death in fetuses with T21 (LR= 4.29; 95CI=1.9-8.0, p<0.0001. In fetuses with 45X, the presence of echocardiographic abnormalities was associated with lower risk of FD (LR= 0.56; 95CI=0.27- 0.85, p=0.005. No predictive factors were identified in the T13/18 group. Intra- uterine lethality of aneuploid fetuses is high. Occurrence of hydrops increases risk of FD in pregnancies with T21. In pregnancies with 45X, the occurrence of echocardiographic changes reduces this risk.

  5. Individualized choice in prenatal diagnosis : the impact of karyotyping and standalone rapid aneuploidy detection on quality of life

    NARCIS (Netherlands)

    Boormans, E. M. A.; Birnie, E.; Oepkes, D.; Boekkooi, P. F.; Bonsel, G. J.; van Lith, J. M. M.

    2010-01-01

    Objective To assess the reasons and perceptions of women who are offered a choice between karyotyping and standalone rapid aneuploidy detection (RAD) and to compare the impact of both tests on anxiety and health-related quality of life Methods In this prospective comparative study, women undergoing

  6. BACs-on-Beads Technology: A Reliable Test for Rapid Detection of Aneuploidies and Microdeletions in Prenatal Diagnosis

    Directory of Open Access Journals (Sweden)

    Sandra García-Herrero

    2014-01-01

    Full Text Available The risk of fetal aneuploidies is usually estimated based on high resolution ultrasound combined with biochemical determination of criterion in maternal blood, with invasive procedures offered to the population at risk. The purpose of this study was to investigate the effectiveness of a new rapid aneuploidy screening test on amniotic fluid (AF or chorionic villus (CV samples based on BACs-on-Beads (BoBs technology and to compare the results with classical karyotyping by Giemsa banding (G-banding of cultured cells in metaphase as the gold standard technique. The prenatal-BoBs kit was used to study aneuploidies involving chromosomes 13, 18, 21, X, and Y as well as nine microdeletion syndromes in 321 AF and 43 CV samples. G-banding of metaphase cultured cells was performed concomitantly for all prenatal samples. A microarray-based comparative genomic hybridization (aCGH was also carried out in a subset of samples. Prenatal-BoBs results were widely confirmed by classical karyotyping. Only six karyotype findings were not identified by Prenatal-BoBs, all of them due to the known limitations of the technique. In summary, the BACs-on-Beads technology was an accurate, robust, and efficient method for the rapid diagnosis of common aneuploidies and microdeletion syndromes in prenatal samples.

  7. 获得性21三体恶性血液病的临床和细胞遗传学特征%Clinical and cytogenetic features of hematologic malignancies associated with acquired trisomy 21

    Institute of Scientific and Technical Information of China (English)

    王焕萍; 倪万茂; 陈志妹; 楼基余; 徐欢; 俞运彪; 钱文斌; 金洁

    2008-01-01

    目的 分析21三体恶性血液病患者的临床及细胞遗传学特点.方法 采用骨髓直接法和(或)培养法制备染色体标本,采用R显带技术进行核型分析,并进行临床随访.结果 共发现25例患者存在21三体,其中急性髓系白血病(acute myeloid leukemia,AML)13例,占同期进行染色体检查的AML患者总数的1.5%,包括M5h6例;急性淋巴细胞(acute lymphoblastic leukemia,ALL)8例,占同期进行染色体检查的ALL患者总数的2.2%,其它类型4例.25例中13例为单纯获得性21三体,其余病例均合并其它异常.随访的19例患者的中位生存期为9个月.结论 单纯21三体在AML中以M5b多见,伴21三体异常的恶性血液病预后还存在争议.%Objective To investigate the association between trisomy 21 abnormalities and the clinical and cytogenetie features of hematologic malignancies. Methods Chromosome preparations were made on bone marrow cells by using direct method and/or unstimulated short-term cultures. Karyotypes were analyzed by R-banding. Results Thirteen patients (1.5 % ) with acute myeloid leukemia (AML) including 6 cases of M5b,8 (2.2 % ) with acute lymphoblastie leukemia (ALL) and4 cases with other hematologic malignancies had aquired trisomy 21, and in 13 patients it oceurred as the sole eytogenetic abnormality. The remaining had combination with other abnormalities. The median survival for the 19 patients with trisomy 21 was 9 months. Conclusion M5b was the major type in AML with sole acquired trisomy 21. Trisomy 21 as the sole abnormality appeared to have a poor prognosis.

  8. Fetal outcome of trisomy 18 diagnosed after 22 weeks of gestation: Experience of 123 cases at a single perinatal center.

    Science.gov (United States)

    Nagase, Hiromi; Ishikawa, Hiroshi; Toyoshima, Katsuaki; Itani, Yasufumi; Furuya, Noritaka; Kurosawa, Kenji; Hirahara, Fumiki; Yamanaka, Michiko

    2016-01-01

    To investigate the pregnancy outcome of the fetuses with trisomy 18, we studied 123 cases of trisomy 18 who were born at our hospital from 1993 to 2009. Among them, 95.9% were diagnosed with trisomy 18 prenatally. Prenatal ultrasound findings showed fetal growth restriction in 77.2%, polyhydramnios in 63.4% and congenital heart defects in 95.1%. For 18 cases, cesarean section (C-section) was chosen, and for 75 cases, transvaginal delivery was chosen. Premature delivery occurred in 35.5%. Stillbirths occurred in 50 cases (40.7%). Fetal demise before onset of labor occurred in 30 cases and fetal demise during labor occurred in 20 cases which was 26.7% of vaginal deliveries. Among the 73 live-born infants, the survival rate for 24 h, 1 week, 1 month and 1 year were 63%, 43%, 33% and 3%. The median survival time was 3.5 days. There was no significant difference between the survival time of C-section and that of vaginal delivery. However, for the births involving breech presentation, the survival time of C-section was significantly longer than that of vaginal delivery. When the fetus is diagnosed with trisomy 18, the parents have to make many choices. These findings constitute critical information in prenatal counseling to the couples whose fetuses have been found to have trisomy 18, especially when they choose palliative approaches in the perinatal management. PMID:26104883

  9. Noninvasive prenatal testing using a novel analysis pipeline to screen for all autosomal fetal aneuploidies improves pregnancy management

    NARCIS (Netherlands)

    Bayindir, Baran; Dehaspe, Luc; Brison, Nathalie; Brady, Paul; Ardui, Simon; Kammoun, Molka; van der Veken, Lars; Lichtenbelt, Klaske; van den Bogaert, Kris; van Houdt, Jeroen; Peeters, Hilde; van Esch, Hilde; de Ravel, Thomy; Legius, Eric; Devriendt, Koen; Vermeesch, Joris R.

    2015-01-01

    Noninvasive prenatal testing by massive parallel sequencing of maternal plasma DNA has rapidly been adopted as a mainstream method for detection of fetal trisomy 21, 18 and 13. Despite the relative high accuracy of current NIPT testing, a substantial number of false-positive and false-negative test

  10. Impact of Trisomy 8 on Cytobiological and Clinical Features of Acute Myelomonocytic and Monocytic Leukemia%8号染色体三体对急性粒、单核细胞白血病细胞生物学和临床特征的影响

    Institute of Scientific and Technical Information of China (English)

    田蕾; 刘凌波; 王晓蓓; 肖娟; 邹萍

    2005-01-01

    为了探讨8号染色体三体(8三体)对急性粒单、单核细胞白血病(M4、M5)细胞生物学及临床特征的影响,应用G显带或R显带技术及流式细胞仪对56例M4、M5患者进行核型及免疫表型检测,并对其临床特征进行回顾性分析.结果表明:56例患者中34例(60.7%)正常核型;10例(17.9%)8三体异常核型,其中3例(5.4%)为单纯8三体核型,余下12例(21.4%)为其他异常核型(不包括8三体).8三体患者的年龄偏大,外周血原始+幼稚细胞百分比和外周血白细胞(WBC)计数均较低,无病生存期(DFS)较短(P均<0.05).8三体患者CD34、CD117和CD56的表达频率较高,而CD11b、CD14和CD15则较低(P分别<0.01、0.05、0.05、0.01、0.05和0.005).结论:8三体的M4、M5患者预后较差,8三体可能与单核细胞分化成熟受抑有关.%To evaluate the impact of trisomy 8 on cytobiological and clinical features of acute myelomonocytic and monocytic leukemia ( M4, M5 ), a total of 56 cases of acute myelomonocytic and monocytic leukemia were investigated.Karyotypes were analyzed by G-banding or R-banding. The immunotypes in all cases were detected by flow cytometry.And the clinical characteristics at the first visit were analyzed retrospectively. The results showed that thirty-four of 56(60.7%) patients had normal cytogenetics; 10 (17.9%) patients had trisomy 8 in their karyotypes, including 3(5.4%) patients with trisomy 8 as the sole aberration; and 12 (21.4%) patents had other cytogenetic abnormalities (except trisomy 8). All trisomy 8 cases demonstrated a increased expression frequency of surface markers of myeloid progenitor cells CD34 (P < 0.01 ) and CD117 ( P < 0.05 ) and a decreased expression frequency of surface markers of mature monocytes CD11c (P < 0.01 ) and CD14 (P < 0.05 ), compared with normal cytogenetics cases. Patients with trisomy 8 were slightly older ( P < 0.05 ), which had lower percentages of peripheral blasts ( P < 0.05 ) and lower WBC ( P

  11. Correlation study between sperm concentration, hyaluronic acid-binding capacity and sperm aneuploidy in Hungarian patients.

    Science.gov (United States)

    Mokánszki, Attila; Molnár, Zsuzsanna; Ujfalusi, Anikó; Balogh, Erzsébet; Bazsáné, Zsuzsa Kassai; Varga, Attila; Jakab, Attila; Oláh, Éva

    2012-12-01

    Infertile men with low sperm concentration and/or less motile spermatozoa have an increased risk of producing aneuploid spermatozoa. Selecting spermatozoa by hyaluronic acid (HA) binding may reduce genetic risks such as chromosomal rearrangements and numerical aberrations. Fluorescence in-situ hybridization (FISH) has been used to evaluate the presence of aneuploidies. This study examined spermatozoa of 10 oligozoospermic, 9 asthenozoospermic, 9 oligoasthenozoospermic and 17 normozoospermic men by HA binding and FISH. Mean percentage of HA-bound spermatozoa in the normozoospermic group was 81%, which was significantly higher than in the oligozoospermic (Psex chromosomes (P=0.014) and chromosome 17 (P=0.0019), diploidy (P=0.03) and estimated numerical chromosome aberrations (P=0.004) were significantly higher in the oligoasthenozoospermic group compared with the other groups. There were statistically significant relationships (Pchromosome aberrations (r=-0.668) and between HA binding and estimated numerical chromosome aberrations (r=-0.682). HA binding and aneuploidy studies of spermatozoa in individual cases allow prediction of reproductive prognosis and provision of appropriate genetic counselling. Infertile men with normal karyotypes and low sperm concentrations and/or less motile spermatozoa have significantly increased risks of producing aneuploid (diminished mature) spermatozoa. Selecting spermatozoa by hyaluronic acid (HA) binding, based on a binding between sperm receptors for zona pellucida and HA, may reduce the potential genetic risks such as chromosomal rearrangements and numerical aberrations. In the present study we examined sperm samples of 45 men with different sperm parameters by HA-binding assay and fluorescence in-situ hybridization (FISH). Mean percentage of HA-bound spermatozoa in the normozoospermic group was significantly higher than the oligozoospermic, the asthenozoospermic and the oligoasthenozoospermic groups. Using FISH, disomy of sex

  12. HLA and trisomy 21. Confirmation of a trend of restricted HLA heterogeneity in parents of Down syndrome children.

    Science.gov (United States)

    Aymé, S; Mercier, P; Dallest, R; Mattei, J F

    1984-03-01

    As the HLA system could play a role in the in utero selection process against abnormal fetuses, HLA-A and -B antigens were evidenced in 30 children with trisomy 21 and in their parents, using a standard microlymphocytotoxicity test. The comparison group included 60 families among whom 39 had HLA typing for paternity exclusion and 21 had been previously selected for a segregation study. Both groups consisted of nonconsanguineous Caucasians from the same geographical area. The Down syndrome (DS) children did not show a significant association with a specific HLA antigen. However, six out of 30 couples having a DS child showed two antigens shared at the A and/or B locus, compared to seven out of 60 control couples. The shared parental antigens were not selectively inherited, and the proportion of homozygote children at one locus was lower for DS (5/30) than for controls (13/60). These findings demonstrate the same trend as previously published but need to be confirmed by other investigators. Perhaps a strong selective pressure in favor of heterozygotes contributes to a better survival rate, as suggested from histocompatibility studies in animals.

  13. Analysis on the sonographic findings of fetuses with trisomy 18 during the second trimester of pregnancy%18-三体综合征胎儿孕中期超声表现分析

    Institute of Scientific and Technical Information of China (English)

    黎新艳; 田晓先; 黄飞雪; 林莲恩; 李雪芹; 周旋

    2011-01-01

    目的:分析18-三体综合征胎儿的中孕期超声表现,探讨其在产前诊断中的作用.方法:对2006年1月~2011年3月在广西壮族自治区妇幼保健院经产前诊断发现的32例中孕期18-三体综合征胎儿进行回顾性分析.结果:32例18-三体综合征胎儿均具有各种不同的高危因素,其中31例有超声异常发现(96.9%),最多见的超声异常为:心脏畸形(50.0%)、肢体畸形(43.8%)、脉络丛囊肿(40.6%)、官内发育迟缓(37.5%);29例(90.6%) 18-三体综合征胎儿可检出两项及以上超声异常,18例(56.3%)可检出4项及以上超声异常.结论:绝大部分的18-三体综合征胎儿中孕期可发现超声异常并以多项异常为主,超声系统检查是最有效的18-三体综合征胎儿产前筛查方法,对胎儿进行中孕期超声系统检查并结合各种高危因素进行综合评价,可减少不必要的侵入性检查.%Objective; To analyze the sonographic findings of fetuses with trisomy 18 during the second trimester of pregnancy, ex-plore its effect in prenatal diagnosis. Methods: 32 fetuses who were diagnosed as trisomy 18 during the second trimester of pregnancy in pre-natal diagnosis in the hospital from January 2006 to March 2011 were analyzed retrospectively. Results; 32 fetuses with trisomy 18 had differ-ent high risk factors, 31 fetuses (96. 9% ) were found with abnormal sonographic findings, the most common abnormal sonographic findings included cardiac defects ( SO. 0% ) , limb deformity ( 43. 8% ) , choroid plexus cysts (40. 6% ) and intrauterine growth retardation (37.5%); 29 fetuses (90.6%) with trisomy 18 were found with two or more than two anomalies detected by ultrasound, 18 fetuses (56.3% ) with trisomy 18 were found with four or more than four anomalies detected by ultrasound. Conclusion; Hie most of the fetuses with trisomy 18 can be found with sonographic abnormalities during the second trimester of pregnancy, and most of them have multiple

  14. 18-三体综合征胎儿产前超声表现分析%Analysis the Prenatal Ultrasonography Manifestation of Trisomy 18 Syndrome

    Institute of Scientific and Technical Information of China (English)

    张征

    2015-01-01

    Objective To explore the sonographic appearances of fetuses with trisomy 18 syndromeand the clinical significance.MethodsThe ultrasound ifndings of 24 cases of trisomy 18 conifrmedby amniocentesis or cordocentesis were evaluated.Results 24 cases had at least 2 parts ofsonographicanomalie, fetal cardiac anomalies were the most common among all the cases, the less abnormal sonographic findings included choroid plexus cysts, short limbsmeasurement or abnormal gestures, polyhydramnios,the other abnormal sonographic findings included fetalgrowth restriction, singleumbilical artery, fetal head in the shape of strawberry, omphalocele, esophagealatresia, absence of the corpus callosum. Dandy—Walker syndrome, ventriculomegaly,abnormal systolic/diastolic ratio (S/D) of umbilical artery,umbilical cord cyst, diaphragmatichernia. ConclusionThe evaluationof prenatal ultrasound screening is effective for the prenatal diagnosis fetus with trisomy 18 conifrmed.%目的探讨18-三体综合症胎儿的产前超声表现及超声检查临床价值。方法回顾性分析24例经羊膜腔穿刺或脐血穿刺染色体核型检查确诊为18-三体综合征胎儿的超声表现。结果确诊的24例18-三体综合征胎儿均有两个及以上异常超声表现,常见超声表现主要为心脏畸形,其次是脉络丛囊肿,四肢骨骼或姿势异常,羊水多,还可见到胎儿生长受限,单脐动脉,草莓头,脐膨出,食道闭锁,胼胝体缺失、Dandy-Walker畸形、侧脑室扩张、脐动脉血流S/D升高、脐带囊肿1例、膈疝等。结论产前超声筛查对18-三体综合征胎儿的产前检出具有重要意义。

  15. 18-三体综合征胎儿产前超声表现分析%Prenatal ultrasonography associated with fetuses of trisomy 18 syndrome

    Institute of Scientific and Technical Information of China (English)

    韩璐; 于华; 荆春丽; 冯丽云; 王彦

    2015-01-01

    Objective:To investigate the sonographic appearances of fetuses with trisomy 18 syndrome and the clinical significance. Methods: The ultrasound findings of 20 cases of trisomy 18 confirmed by amniocentesis or cordocentesis were evaluated.Results: All of the 20 cases had at least 2 parts of sonographicanomalies. Fetal cardiac anomalies were the most common ifndings which accounted for 75%among all the cases. The less abnormal sonographic findings included choroid plexus cysts, short limbs measurement or abnormal gestures, polyhydramnios, The other abnormal sonographic ifndings included fetal growth restriction, singleumbilical artery, fetal head in the shape of strawberry, omphalocele, esophageal atresia,absence of the corpus callosum,Dandy—Walker syndrome,ventriculomegaly,abnormal systolic/diastolic ratio(S/D)of umbilical artery,umbilical cord cyst,diaphragmatichernia.Conclusion:The evaluation of prenatal ultrasound screening is effective for the Prenatal diagnosis fetus with trisomy 18.%目的:探讨18-三体综合症胎儿的产前超声表现及超声检查临床价值。方法:回顾性分析20例经羊膜腔穿刺或脐血穿刺染色体核型检查确诊为18-三体综合征胎儿的超声表现。结果:确诊的20例18-三体综合征胎儿均有两个及以上异常超声表现,常见超声表现主要为心脏畸形15例(75%),其次是脉络丛囊肿,四肢骨骼或姿势异常,羊水多,还可见到胎儿生长受限,单脐动脉,草莓头,脐膨出,食道闭锁,胼胝体缺失、Dandy-Walker畸形、侧脑室扩张、脐动脉血流S/D升高、脐带囊肿1例、膈疝等。结论:产前超声筛查对18-三体综合征胎儿的产前检出具有重要意义。

  16. Rapid detection of chromosome 18 aneuploidies in amniocytes by using primed in situ labeling (PRINS) technique

    Institute of Scientific and Technical Information of China (English)

    杨建滨; 郑树

    2002-01-01

    This paper presents a feasible method for rapid detection of the interphase nuclei of uncultured amniocytes for chromosomes 18 by using our modified primed in situ labeling (PRINS) technique. A total of 262 independent, uncultured amniotic fluid samples were analysed in a blind fashion before the karyotype was available. In addition, 62 samples were examined by fluorescence in situ hybridization (FISH) for comparison. In more than 95% of the samples PRINS reactions with primer 18cen were successfully induced. Two samples were properly identified and correctly scored as trisomic 18. PRINS reaction could be performed automatically in less than one hour with a programmable thermocycler. Our studies showed that the PRINS technique is simple, rapid and cost-effective. It is as sensitive and specific as FISH; can enhance the accuracy of standard cytogenetic analysis; and allows identification of chromosomes 18 aneuploidies in uncultured amniocytes in significantly less time.

  17. Suppression of allelic recombination and aneuploidy by cohesin is independent of Chk1 in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Shay Covo

    Full Text Available Sister chromatid cohesion (SCC, which is established during DNA replication, ensures genome stability. Establishment of SCC is inhibited in G2. However, this inhibition is relived and SCC is established as a response to DNA damage, a process known as Damage Induced Cohesion (DIC. In yeast, Chk1, which is a kinase that functions in DNA damage signal transduction, is considered an activator of SCC through DIC. Nonetheless, here we show that, unlike SCC mutations, loss of CHK1 did not increase spontaneous or damage-induced allelic recombination or aneuploidy. We suggest that Chk1 has a redundant role in the control of DIC or that DIC is redundant for maintaining genome stability.

  18. Suppression of Allelic Recombination and Aneuploidy by Cohesin Is Independent of Chk1 in Saccharomyces cerevisiae

    Science.gov (United States)

    Gordenin, Dmitry A.; Resnick, Michael A.

    2014-01-01

    Sister chromatid cohesion (SCC), which is established during DNA replication, ensures genome stability. Establishment of SCC is inhibited in G2. However, this inhibition is relived and SCC is established as a response to DNA damage, a process known as Damage Induced Cohesion (DIC). In yeast, Chk1, which is a kinase that functions in DNA damage signal transduction, is considered an activator of SCC through DIC. Nonetheless, here we show that, unlike SCC mutations, loss of CHK1 did not increase spontaneous or damage-induced allelic recombination or aneuploidy. We suggest that Chk1 has a redundant role in the control of DIC or that DIC is redundant for maintaining genome stability. PMID:25551702

  19. Telomere shortening correlates to dysplasia but not to DNA aneuploidy in longstanding ulcerative colitis

    DEFF Research Database (Denmark)

    Friis-Ottessen, Mariann; Bendix, Laila; Kølvraa, Steen;

    2014-01-01

    Ulcerative colitis (UC) is a chronic, inflammatory bowel disease which may lead to dysplasia and adenocarcinoma in patients when long-lasting. Short telomeres have been reported in mucosal cells of UC patients. Telomeres are repetitive base sequences capping the ends of linear chromosomes, and pr...... shortening of one or more telomeres to a critical length, rather than bulk shortening of telomeres, seems to be associated with chromosomal instability.......Ulcerative colitis (UC) is a chronic, inflammatory bowel disease which may lead to dysplasia and adenocarcinoma in patients when long-lasting. Short telomeres have been reported in mucosal cells of UC patients. Telomeres are repetitive base sequences capping the ends of linear chromosomes......, and protect them from erosion and subsequent wrongful recombination and end-to-end joining during cell division. Short telomeres are associated with the development of chromosomal instability and aneuploidy, the latter being risk factors for development of dysplasia and cancer. Specifically, the abrupt...

  20. The feasibility study of non-invasive fetal trisomy 18 and 21 detection with semiconductor sequencing platform.

    Directory of Open Access Journals (Sweden)

    Young Joo Jeon

    Full Text Available OBJECTIVE: Recent non-invasive prenatal testing (NIPT technologies are based on next-generation sequencing (NGS. NGS allows rapid and effective clinical diagnoses to be determined with two common sequencing systems: Illumina and Ion Torrent platforms. The majority of NIPT technology is associated with Illumina platform. We investigated whether fetal trisomy 18 and 21 were sensitively and specifically detectable by semiconductor sequencer: Ion Proton. METHODS: From March 2012 to October 2013, we enrolled 155 pregnant women with fetuses who were diagnosed as high risk of fetal defects at Xiamen Maternal & Child Health Care Hospital (Xiamen, Fujian, China. Adapter-ligated DNA libraries were analyzed by the Ion Proton™ System (Life Technologies, Grand Island, NY, USA with an average 0.3× sequencing coverage per nucleotide. Average total raw reads per sample was 6.5 million and mean rate of uniquely mapped reads was 59.0%. The results of this study were derived from BWA mapping. Z-score was used for fetal trisomy 18 and 21 detection. RESULTS: Interactive dot diagrams showed the minimal z-score values to discriminate negative versus positive cases of fetal trisomy 18 and 21. For fetal trisomy 18, the minimal z-score value of 2.459 showed 100% positive predictive and negative predictive values. The minimal z-score of 2.566 was used to classify negative versus positive cases of fetal trisomy 21. CONCLUSION: These results provide the evidence that fetal trisomy 18 and 21 detection can be performed with semiconductor sequencer. Our data also suggest that a prospective study should be performed with a larger cohort of clinically diverse obstetrics patients.

  1. Double trisomy mosaic (47,XXX/48,XXX,+13) confirmed by FISH and skin fibroblast culture

    Energy Technology Data Exchange (ETDEWEB)

    Lieber, E.; Grady, V.; Dosik, H. [Interfaith Medical Center, Brooklyn, NY (United States)] [and others

    1994-09-01

    A 4 lb 8 oz female was born to a 49-year-old woman (P1200G12) at 40 weeks. The baby had tetralogy of Fallot, polydactyly, microcephaly, low set simple ears, posterior cleft of the soft palate and overlapping flexion deformities of both hands. The eyes were deep set. The clinical impression was trisomy 13. The baby is not doing well and needs a gastrotomy tube for feeding. Sucking is allright but swallowing is impeded. An MRI showed an anomaly of the corpus callosum. The ophthalmological examination showed no abnormalities. A chromosome study on a 2-day peripheral blood sample resulted in poor growth and poor morphology; however, 20 Giemsa-banded cells revealed a 47,XXX karyotype. A second specimen was obtained to search for mosaicism and a blood smear revealed nuclear projections on the neutrophils. FISH analysis using whole chromosome painting probe (Life Technologies) first identified the extra chromosome number 13, the final results showing five of sixty metaphase cells (8.3%) with trisomy 13. Cytogenetic analysis using Giemsa-banding technique revealed four cells in fifty examined (8.0%) with a 48,XXX,+13 karyotype. In order to further evaluate the mosaicism, cytogenetic analysis of a skin fibroblast culture was performed. Twenty one of twenty three cells examined (91.3%) showed the 48,XXX,+13 karyotype. FISH analysis of the skin biopsy revealed eighteen of twenty cells (90.9%) with the trisomy 13. The FISH technique is an important enhancement to routine cytogenetic studies when they do not immediately correlate with clinical impressions.

  2. Chromosomal aberrations and aneuploidy in oral potentially malignant lesions: distinctive features for tongue

    Directory of Open Access Journals (Sweden)

    Castagnola Patrizio

    2011-10-01

    Full Text Available Abstract Background The mucosae of the oral cavity are different at the histological level but appear all equally exposed to common genotoxic agents. As a result of this exposure, changes in the mucosal epithelia may develop giving rise to Oral Potentially Malignant Lesions (OPMLs, which with time may in turn progress to Oral Squamous Cell Carcinomas (OSCCs. Therefore, much effort should be devoted to identify features able to predict the likeliness of progression associated with an OPML. Such features may be helpful in assisting the clinician to establish both appropriate therapies and follow-up schedules. Here, we report a pilot study that compared the occurrence of DNA aneuploidy and chromosomal copy number aberrations (CNAs in the OPMLs from different oral anatomical subsites. Methods Samples from histologically diagnosed OPMLs were processed for high resolution DNA flow cytometry (hr DNA-FCM in order to determine the relative DNA content expressed by the DNA index (DI. Additionally, array-Comparative Genomic Hybridization (a-CGH analysis was performed on DNA obtained from diploid nuclei suspensions directly. When aneuploid nuclei were detected, these were physically separated from diploid nuclei on the base of their DI values by means of a DNA-FCM-Sorter in order to improve the a-CGH analysis. Results Tongue OPMLs were more frequently associated with DNA aneuploidy and CNAs than OPMLs arising from all the other mucosal subsites. Conclusions We suggest that the follow-up and the management of the patients with tongue OPMLs should receive a distinctive special attention. Clearly, this hypothesis should be validated in a prospective clinical study.

  3. Heterotopic ossification after patellar tendon repair in a man with trisomy 8 mosaicism: a case report and literature review

    Directory of Open Access Journals (Sweden)

    Chmell Samuel

    2011-09-01

    Full Text Available Abstract Introduction Heterotopic ossification is the abnormal formation of lamellar bone in soft tissue. Its presence jeopardizes functional outcome, impairs rehabilitation and increases costs due to subsequent surgical interventions. Case presentation We present a case of a 32-year-old African-American man with trisomy 8 mosaicism who developed severe heterotopic ossification of his right extensor mechanism subsequent to repair of a patellar tendon rupture. Conclusion To the best of our knowledge there are no prior reports of heterotopic ossification as a complication of patellar tendon repair. This case may suggest an association between trisomy 8 mosaicism and increased risk of heterotopic ossification.

  4. Unique mosaicism of tetraploidy and trisomy 8: Clinical, cytogenetic, and molecular findings in a live-born infant

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, H.E.; Saxe, D.F.; Muralidharan, K. [Emory Univ. School of Medicine, Atlanta, GA (United States)] [and others

    1996-03-29

    We report on a live-born infant with mosaicism of tetraploidy and trisomy 8 who had craniofacial abnormalities, cardiac and genitourinary defects, agenesis of the corpus callosum, and anomalies of limbs. The infant died at age 14 weeks. Molecular studies were done on peripheral blood lymphocytes and cultured amniocytes to determine the origin of the cytogenetic abnormalities. On the basis of the results, we describe a possible mechanism to explain these abnormalities. To our knowledge, this infant represents the first reported case of mosaic trisomy 8 with a tetraploid cell line. 14 refs., 4 figs., 2 tabs.

  5. Follow-up of infants with amniotic fluid trisomy 20 mosaicism.

    Science.gov (United States)

    Abuelo, D N; Barsel-Bowers, G; Zartler, A S

    1986-07-01

    The finding of trisomy 20 mosaicism in amniotic fluid is a cause of considerable anxiety for both physicians and parents. Although the significance of this finding is still not clear, some reassurance can be given to prospective parents, since the outcome has been normal in all reported pregnancies carried to term. Follow-up information on psychomotor development of these infants is needed in order to provide better genetic counseling to these families. We have followed three infants who have had normal growth and psychomotor development up to approximately 2 years.

  6. Temporal bone histopathology in trisomy 18 syndrome: a report of two cases.

    Directory of Open Access Journals (Sweden)

    Saito,Ryusuke

    1987-06-01

    Full Text Available Temporal bone histopathological findings of two patients with trisomy 18 syndrome are described. Many of the abnormalities previously described were seen in the present cases; namely, atresia of the external auditory canal, aberrant course of the tensor tympani muscle, malformed stapes, aberrant course of the facial nerve with an obtuse angulation at the first genu and displacement of geniculate ganglion cells into the internal auditory canal, shortened cochlea with decreased spiral ganglion cell population, and vestibular anomalies, such as bony and membranous blockage of the superior semicircular canal. Moreover, an extremely underdeveloped malleus and incus continuous with a persistent Meckel's cartilage were observed.

  7. Derivation of Trisomy 21 affected human embryonic stem cell line Genea021.

    Science.gov (United States)

    Dumevska, Biljana; Bosman, Alexis; McKernan, Robert; Main, Heather; Schmidt, Uli; Peura, Teija

    2016-03-01

    The Genea021 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Trisomy 21, indicative of Down Syndrome. Following ICM outgrowth on inactivated human feeders, CGH and STR analyses demonstrated a 47, XY, +21 karyotype and male allele pattern. The hESC line had pluripotent cell morphology, 71% of cells expressed Nanog, 84% Oct4, 23% Tra1-60 and 95% SSEA4, gave a Pluritest Pluripotency score of 21.85, Novelty of 1.42, demonstrated Alkaline Phosphatase activity and tri-lineage teratoma formation. The cell line was negative for Mycoplasma and visible contamination. PMID:27346003

  8. Derivation of Trisomy 21 affected human embryonic stem cell line Genea021

    Directory of Open Access Journals (Sweden)

    Biljana Dumevska

    2016-03-01

    Full Text Available The Genea021 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Trisomy 21, indicative of Down Syndrome. Following ICM outgrowth on inactivated human feeders, CGH and STR analyses demonstrated a 47, XY, +21 karyotype and male allele pattern. The hESC line had pluripotent cell morphology, 71% of cells expressed Nanog, 84% Oct4, 23% Tra1–60 and 95% SSEA4, gave a Pluritest Pluripotency score of 21.85, Novelty of 1.42, demonstrated Alkaline Phosphatase activity and tri-lineage teratoma formation. The cell line was negative for Mycoplasma and visible contamination.

  9. Analysis of sonographic features of trisomy 18%18-三体综合征胎儿超声声像特征分析

    Institute of Scientific and Technical Information of China (English)

    沈国芳; 姜立新; 应涛

    2011-01-01

    Objective To evaluate the sonographic characteristics of fetus with trisomy 18. Methods The results of ultrasound findings of 12 cases of trisomy 18 were reviewed. Results All cases had at least two abnormal sonographic findings. Fetal growth restriction and polyhydramnios were the most common findings (58. 3%) followed by cardiac anomalies (50%). Other common sonographic findings included choroid plexus cysts, single umblical artery, lateloencephalia and preaxial upper limb reduction. For those less than 28 gastations, cardiac anomalies and choroid plexus cysts were the commonest (66. 7%), then were polyhydramnios and fetal growth restriction (50%). Conclusion Detailed ultrasound can effectively screen fetus with trisomy 18.%目的 分析18-三体综合征胎儿超声声像特征,以期早期诊断与处理.方法 回顾分析经染色体核型分析确诊的18-三体儿12例超声检查的资料.结果 全部18-三体儿存在二个或以上异常超声声像表现.其中,胎儿生长受限、羊水过多表现率最高,各为58.3%;其次是心脏畸形,50.0%;再其次是脉络丛囊肿、单脐动脉、脑发育不全、上肢发育异常.在<228周的胎儿中,超声异常的表现率最高的是心脏畸形、脉络丛囊肿,各为66.7%,其次是胎儿生长受限、羊水过多,各为50.0%.胎儿生长受限主要表现为股骨长度发育落后于正常.结论 超声检查是产前筛查18-三体儿的有效手段.

  10. Analysis of prenatal sonographic features in fetus with trisomy 18%18-三体综合征胎儿产前超声特征分析

    Institute of Scientific and Technical Information of China (English)

    钟晓红; 谢小健; 吴幼平; 何晓琴; 张艳红; 路晶; 阮爱花

    2012-01-01

    Objective To study the prenatal sonographic features in fetuses with trisomy 18. Methods The ultrasonography findings of 54 fetuses with trisomy 18 confirmed by amniocentesis and cordocentesis were reviewed and the ultrasonogram characteristics of trisomy 18 were summarized. Results Forty-eight cases( 88.9%, 48/54) of 54 fetuses with trisomy 18 had abnormal sonographic finding. Among 33 cases, at least two abnormalities were found simultaneously(61.1%, 33/54). Cardiac defects were the most common findings which accounted for 62.9% among all the cases. The less abnormal sonographic findings included choroid plexus cysts, single umbilical artery, polyhydramnios, echogenic intracardiac focous, short limbs measurements or abnormal gestures, cleft of lip and palate, mild hydronephrosis, The other abnoumal findings included omphalocele, Dandy-Walker syndrome, atresia esophagus,intrauterine growth retardation(IUGR), and so on. The above abnormal findings were indicated by prenatal ultrasonography. The ventricular septal defect combined with abnormal gesturesar micrognathia was found in 3 cases, mandibular micrognathia was showed in 2 cases and 1 case with low-set, malformed ears were not diagnosed by prenatal ultrasonography. Conclusion Prenatal ultrasonography is helpful to find the abnormalities in fetus with trisony 18, which are significant for clinical diagnosis.%目的 探讨18-三体综合征胎儿的产前超声声像图特征.方法 回顾性分析经染色体核型分析确诊为18-三体综合征的54例胎儿声像图表现,总结归纳18-三体综合征胎儿产前超声表现特点.结果 54例18-三体综合征胎儿中,48例(88.9%)产前有异常超声表现,33例(61.1%,33/54)合并两种以上异常,最多见的为心脏畸形,共34例,占62.9%;其次有脉络丛囊肿、单脐动脉、羊水量过多、心室斑状强回声、四肢骨骼或姿势异常、唇腭裂、肾盂分离,其他异常表现还有脐膨出、Dandy-Walker综合征、食道

  11. Management Considerations for Ongoing Pregnancies Complicated by Trisomy 13 and 18.

    Science.gov (United States)

    Dotters-Katz, Sarah K; Kuller, Jeffrey A; Grace, Matthew R; Laifer, Steven A; Strauss, Robert A

    2016-05-01

    Pregnancies complicated by trisomy 13 (T13) or trisomy 18 (T18) present unique challenges for obstetric management. From the initial diagnosis, the task of counseling these women and families is difficult because fetal and neonatal outcomes vary depending on the phenotype and degree of intervention chosen by the family. A literature review was performed using PubMed to gather information regarding obstetric management and outcomes of pregnancies complicated by T13 and T18. Spontaneous abortion and in uterofetal demise occur at rates well above those seen in chromosomally normal pregnancies. In addition, infants with T13 or T18 frequently have structural anomalies, which lead to worse prognoses and long-term survival. In cases in which a woman and her family desire to continue the pregnancy, multidisciplinary consultation with obstetrics, social work, genetics, and pediatrics can optimize care of both the fetus and the mother. Most commonly, prenatal care does not differ from routine. A detailed delivery plan should be generated, specifically discussing interventions for the patient and her fetus. When managing pregnancies complicated by T13 and T18, active, open, and frequent communication between the patient, her family, and a multidisciplinary health care team throughout the pregnancy is crucial. PMID:27182826

  12. Microarray-Based Analysis of Methylation of 1st Trimester Trisomic Placentas from Down Syndrome, Edwards Syndrome and Patau Syndrome

    DEFF Research Database (Denmark)

    Hatt, Lotte; Aagaard, Mads M; Bach, Cathrine;

    2016-01-01

    Methylation-based non-invasive prenatal testing of fetal aneuploidies is an alternative method that could possibly improve fetal aneuploidy diagnosis, especially for trisomy 13(T13) and trisomy 18(T18). Our aim was to study the methylation landscape in placenta DNA from trisomy 13, 18 and 21 preg...

  13. Investigation of the frequency of chromosomal aneuploidy using triple fluorescence in situ hybridization in 12 Chinese infertile men

    Institute of Scientific and Technical Information of China (English)

    张群芳; 卢光琇

    2004-01-01

    Background Chromosomal aberrations are the major cause of pre-and post-implantation embryo wastage and some studies suggest that half of all human conceptions have a chromosomal abnormality. A chromosomal aberration in human sperms is also one of the causes of failure of in vitro fertilization. This study was designed to ascertain whether chromosomal aneuploidy in spermatozoa is a risk factor for male infertility.Methods Twelve infertile men were divided into two groups: 10 with oligoasthenoteratozoospermia (OAT, Group A) and two with a normal semen analysis (Group B). Two normal healthy sperm donors acted as controls (Group C). We used fluorescence in situ hybridization (FISH) and probes for chromosomes X, Y and 18 to determine the frequency of aneuploidy.Results The frequencies of spermatozoa disomy for chromosomes X, Y and 18 were 0.30% and 0.30%, respectively, in Group B. The percentages were not significantly different from those of Group C (0.15% and 0. 16%). The frequencies of nullisomy for chromosomes X, Y and 18 were 0.15%and 0 for Group B, and 0 and 0.15% for Group C (P>0.05). In Group A, the incidences of disomy were 1.13% and 0. 96% and the frequencies of nullisomy were 1.13% and 1.60%. In these three groups, the incidences of diploidy were 0.60%, 1.00%, and 0.30%, respectively. Both the frequencies of disomic and nullisomic spermatozoa for chromosomes X, Y, and 18 and of diploid spermatozoa were significantly higher in Group A than in Groups B and C. The estimated total aneuploidy rates in the sperm from the three groups were 42.44%, 6.05%, and 2.59%,respectively.Conclusion These results indicate that chromosomal aneuploidy in spermatozoa may be a risk factor for infertility.

  14. Prenatal screening for fetal aneuploidies with cell-free DNA in the general pregnancy population: a cost-effectiveness analysis

    OpenAIRE

    Fairbrother, Genevieve; Burigo, John; Sharon, Thomas; Song, Ken

    2015-01-01

    Abstract Objective: To estimate the cost-effectiveness of fetal aneuploidy screening in the general pregnancy population using non-invasive prenatal testing (NIPT) as compared to first trimester combined screening (FTS) with serum markers and NT ultrasound. Methods: Using a decision-analytic model, we estimated the number of fetal T21, T18, and T13 cases identified prenatally, the number of invasive procedures performed, corresponding normal fetus losses, and costs of screening using FTS or N...

  15. Retrospective study of trisomy 18 in chorionic villi with fluorescent in situ hybridization on archival direct preparations

    NARCIS (Netherlands)

    A.R.M. van Opstal (Diane); C.D.F. van den Berg (Cardi); M.G. Jahoda (M.); H. Brandenburg (Helen); F.J. Los; P.A. In't Veld (Peter)

    1995-01-01

    textabstractTrisomy 18 in direct chorionic villus preparations needs further investigation since the chromosome abnormality may be confined to the placenta and may not represent the actual fetal karyotype. We performed, retrospectively, fluorescent in situ hybridization (FISH) with the chromosome 18

  16. Potential use of buccal smears for rapid diagnosis of autosomal trisomy or chromosomal sex in newborn infants using DNA probes

    Energy Technology Data Exchange (ETDEWEB)

    Harris, C.; Clark, K.; Lazarski, K. [Univ. of Wisconsin, Madison, WI (United States); Wilkerson, C. [Univ. of Wisconsin Medical School, Madison, WI (United States); Meisner, L. [Univ. of Wisconsin, Madison, WI (United States)]|[Univ. of Wisconsin Medical School, Madison, WI (United States)

    1994-12-01

    Buccal smears from 3 women and 1 man were probed with alpha satellite DNA probes for chromosomes 8, 18, X, and Y. Buccal smears were also collected from an adolescent phenotypic female with uterine agenesis, as well as from newborn infants with suspected trisomy 18 and trisomy 21. The clinical cases were confirmed with conventional cytogenetic studies of peripheral lymphocytes. Overall probe efficiency at detecting expected chromosome number in interphase cells was found to be 71% {+-} 6.8%. Higher than expected n-1 signal numbers may be due to karyopyknotic intermediate epithelial cells present in all collected samples. Overall probe efficiency was found to be consistent using alpha satellite and cosmid probes, both of which accurately reflected the modal copy number of the target chromosomes. False trisomy was less than 1%. This study suggests DNA probes can be used in buccal smears for rapid diagnosis of trisomies and chromosomal sex in newborns, but because of high rates of false hydropoploid signals, probed buccal smear specimens may not be accurate at diagnosing mosaicism. 9 refs., 2 figs., 1 tab.

  17. First trimester maternal serum concentrations of fetal antigen 2 in normal pregnancies and those affected by trisomy 21

    NARCIS (Netherlands)

    Price, KM; Van Lith, JMM; Silman, R; Mantingh, A; Grudzinskas, JG

    1998-01-01

    Serum concentrations of fetal antigen 2 (FA-2), the amino-propeptide of the al chain of collagen type I, were measured in peripheral blood from women with normal (n = 234) and trisomy 21 affected (n = 14) pregnancies between 9 and 11 weeks gestation. Serum FA-2 concentrations were seen to be stable

  18. Prenatal evaluation of a fetus with trisomy 18 and additional balanced de novo Rob(13;14.

    Directory of Open Access Journals (Sweden)

    R Posmyk

    2010-01-01

    Full Text Available The main aim of this work is to present unusual case with full trisomy 18 and additional robertsonian translocation- Rob (13;14 detected through abnormalities found in prenatal ultrasound examination. A 26 years-old pregnant women with no family history of any reproductive failure underwent level II ultrasound screening in 19 weeks of gestation. Polyhydramnios, intrauterine growth retardation, hydrocephalus, enlarged lateral ventricles, club foot and cardiac defect were found. Amniocentesis was indicated considering the high likelihood of a chromosomal aberration. Abnormal karyotype was detected 46, XY, der(13;14(q10;q10, +18. Karyotypes of parents were normal, what confirmed de novo origin of this aberration. Pregnancy was terminated. In postnatal examination fetus demonstrated intrauterine groth retardation and a lot of dysmorphic features characteristic for trisomy 18: microcephaly, prominent occiput, very low set and posteriorly rotated ears, hypertelorism, small mouth, small recessed mandible, a high narrow palate, broad nasal bridge, low-set ears, preauricilar skin appendage, clenched fingers clinodactyly of Vth fingers and club foot. In conclusion it is worth to say that our described fetus demonstrated rather typical for trisomy 18 ultrasonographic features. Balanced Rob (13;14 gives no phenotypic expression. Possible interchromosomal effect in complex chromosomal aberration formation such as Rob (13;14 with trisomy 18 was discussed.

  19. Neurocognitive Outcomes of Individuals with a Sex Chromosome Trisomy: XXX, XYY, or XXY--A Systematic Review

    Science.gov (United States)

    Leggett, Victoria; Jacobs, Patricia; Nation, Kate; Scerif, Gaia; Bishop, Dorothy V. M.

    2010-01-01

    Aim: To review systematically the neurodevelopmental characteristics of individuals with sex chromosome trisomies (SCTs). Method: A bibliographic search identified English-language articles on SCTs. The focus was on studies unbiased by clinical referral, with power of at least 0.69 to detect an effect size of 1.0. Results: We identified 35…

  20. Meiotic behaviour and sperm aneuploidy in an infertile man with a mosaic 45,X/46,XY karyotype.

    Science.gov (United States)

    Ren, He; Chow, Victor; Ma, Sai

    2015-12-01

    The meiotic behaviour of the germ cells in 45,X/46,XY men has not been extensively studied. This study investigated the meiotic events and sperm aneuploidy in an azoospermic man with a 45,X/46,XY (50/50) mosaic karyotype to better understand the fate of the 45,X cells and the production of chromosomally abnormal spermatozoa. Combining immunofluorescence techniques and fluorescence in-situ hybridization, meiotic recombination, synapsis, meiotic sex chromosome inactivation (MSCI) and configuration were analysed, as well as sperm aneuploidy in the patient and 10 normal, fertile men. Despite the 50:50 somatic mosaicism in the patient, 25% of pachytene cells analysed were 45,X. Furthermore, 63% of pachytene cells were 46,XY with paired sex chromosomes, and 12% were 46,XY with unpaired sex chromosomes, which displayed abnormal MCSI patterns. Although the patient's testicular spermatozoa showed increased aneuploidy, the majority were of normal constitution. The X:Y sperm ratio was significantly increased compared with the controls (P chromosomal constitution despite an individual's abnormal karyotype.

  1. Increased number of sex chromosomes affects height in a nonlinear fashion: a study of 305 patients with sex chromosome aneuploidy

    DEFF Research Database (Denmark)

    Ottesen, Anne-Marie; Aksglaede, Lise; Garn, Inger;

    2010-01-01

    with higher grade sex chromosome aneuploidies. It has been proposed that tall stature in sex chromosome aneuploidy is related to an overexpression of SHOX, although the copy number of SHOX has not been evaluated in previous studies. Our aims were therefore: (1) to assess stature in 305 patients with sex...... chromosome aneuploidy and (2) to determine the number of SHOX copies in a subgroup of these patients (n = 255) these patients and 74 healthy controls. Median height standard deviation scores in 46,XX males (n = 6) were -1.2 (-2.8 to 0.3), +0.9 (-2.2 to +4.6) in 47,XXY (n = 129), +1.3 (-1.8 to +4.9) in 47,XYY......,XXXX (n = 13), and -1.0 (-3.5 to -0.8) in 49,XXXXX (n = 3). Height increased with an increasing number of extra X or Y chromosomes, except in males with five, and in females with four or five sex chromosomes, consistent with a nonlinear effect on height....

  2. Partial monosomy 8q and partial trisomy 9q due to the maternal translocation t(8;9(q24.3;q34.1)

    DEFF Research Database (Denmark)

    Tos, T; Alp, M Y; Eker, H K;

    2014-01-01

    Partial trisomy 9q34-qter and partial monosomy 8q24.3-qter are very rare chromosomal abnormalities. Characteristic features of partial trisomy 9q34-qter are hypotonia, developmental delay, mild intellectual disability, dolichocephaly, distinct facial phenotype, long and thin fingers, and cardiac......, brachycephaly, facial dysmorphism, hand and foot anomalies, bilateral hearing loss, cardiac defect and abnormal brain MRI findings. To the best of our knowledge, this is the first report of the combination of partial trisomy 9q and partial monosomy 8q....

  3. SNP基因芯片结合多重置换扩增技术检测单细胞非整倍体的研究%Detection of Aneuploidy from Single Cells by Array-Comparative Genetic Hybridization

    Institute of Scientific and Technical Information of China (English)

    凌家炜; 方丛; 徐艳文; 庄广伦

    2009-01-01

    [目的] 建立并优化利用微阵列-比较基因组杂交技术检测单细胞非整倍体的实验方案. [方法] 纤维母细胞系GM02732(47,XY,+18)和GM00343[46,XY,4(del) (qter > p14)]被用于实验.阳性对照组为上述细胞系的基因组DNA(gDNA)(A组与B组,n = 6);实验组为单细胞模板的多重置换扩增(MDA)产物(C组与D组,n = 10);阴性对照组为空白对照的MDA产物(E组,n = 6).以上样本与10 k 2.0基因分型芯片杂交并进行染色体拷贝数分析,比较利用非扩增的正常gDNA和同法扩增的DNA(MDA-DNA)作为分析参照对C组和D组的结果准确度的影响.[结果] A→E组的芯片杂交信号判读率分别为98.7%、97.2%、86.7%、85.9%与3.2%.利用单细胞MDA-DNA作为参照时,C组与D组杂交信号的变异程度明显小于使用gDNA作为参照时(P < 0.05).利用CNAT分析软件,发现以gDNA作为参照时,C组与D组部分染色体优势扩增明显,而使用MDA-DNA作为参照时则未观察到类似现象. [结论] 结合MDA和基因芯片平台对单细胞进行非整倍体检测时应使用同法扩增的DNA作为分析参照.%[Objective] To set up an optimized protocol for aneuploidy detection from single cells through Array- Comparative Genetic Hybridization (CGH).[Method] Two cell lines,trisomy 18 (Tri-18;GM02732,47,XY,+18) and chromosome 4 segment deletion [sDel-4;GM00343,46,XY,4(del) (qter > p14)],were used in the study.In combination of 10 k 2.0 SNP mapping array platform and multiple displacement amplification (MDA),the diagnostic accurate rates of MDA product from single cells of the two cell lines using gDNA and single-cell MDA product as reference were compared.[Result] An extremely lower call rate (3.2 ± 1.2)% in the negative control group was observed compared to the experiment groups.When the single-cell MDA product was used as reference,the standard deviations of Log2 (signal intensity ratio) were significantly decreased in both groups,compared with when the g

  4. Hepatic failure, neonatal hemochromatosis and porto-pulmonary hypertension in a newborn with trisomy 21 - a case report

    Directory of Open Access Journals (Sweden)

    Poulik Janet

    2010-05-01

    Full Text Available Abstract Liver failure in neonates is a rare but often fatal disease. Trisomy 21 is not usually associated with significant infantile liver disease. If present, hepatic dysfunction in an infant with Trisomy 21 is likely to be attributed to transient myeloproliferative disorder with hepatic infiltration by hematopoietic elements and may be associated with secondary hemosiderosis. A less commonly recognized cause of liver failure in neonates with Trisomy 21 is neonatal hemochromatosis (NH; this association has been reported in nine cases of Trisomy 21 in literature. NH is a rare, severe liver disease of intra-uterine onset that is characterized by neonatal liver failure and hepatic and extrahepatic iron accumulation that spares the reticuloendothelial system. NH is the most frequently recognized cause of liver failure in neonates and the commonest indication for neonatal liver transplantation. Although porto-pulmonary hypertension (PPH has been reported as a complication of liver failure in adults and older children, this has not been reported in neonates with liver failure of any etiology. This is probably due to the rarity of liver failure in newborns, delayed diagnosis and high mortality. The importance of recognizing PPH is that it is reversible with liver transplantation but at the same time increases the risk of post-operative mortality. Therefore, early diagnosis of PPH is critical so that early intervention can improve the chances of successful liver transplantation. We report for the first time the association of liver failure with porto-pulmonary hypertension secondary to NH in an infant with Trisomy 21.

  5. Large-vessel thrombosis in intestinal Beh(c)et's disease complicated with myelodysplastic syndrome and trisomy 8

    Institute of Scientific and Technical Information of China (English)

    Huang-Chi Chen; Ying-Ming Chiu

    2012-01-01

    Beh(c)et's disease is characterized by recurrent oral ulcers,genital ulcers,uveitis and skin lesions.Myelodysplastic syndrome (MDS) is characterized by problems due to ineffective hematopoiesis.Several studies have identified a relationship between MDS and Beh(c)et's disease,especially intestinal Beh(c)et's disease.Trisomy 8 seems to play an important role in these disorders as well.The present case was a 24-year-old woman who had a huge tonsil ulcer with initial symptoms of odynophagia and intermittent fever.We also noted folliculitis on her upper back.Five days later,she began to experience diarrhea and abdominal pain.Abdominal computed tomography and subsequent surgery revealed ileum perforation and enterocolitis with multiple ulcers.Later,she was admitted again for a vulvar suppurative ulcer and suspicious Bartholin's cyst infection.The patient's clinical presentations met the criteria for Beh(c)et's disease.Six months after the bowel perforation event,we noted the development of pancytopenia in a routine laboratory examination.All the examinations led to the diagnosis of MDS with trisomy 8.The most unusual finding was that multiple large vessel thrombi developed during follow-up.Previous studies have suggested that trisomy 8 in MDS leads to concurrent intestinal Beh(c)et's disease.Moreover,the inflammatory and immune genes related to thrombus formation are overexpressed in cases of MDS with trisomy 8.Trisomy 8 must play a role in thrombosis.Further studies are needed to help clarify the pathophysiology and pathogenesis of these disorders.

  6. Detection of trisomy 7 in bronchial cells from uranium miners

    Energy Technology Data Exchange (ETDEWEB)

    Lechner, J.F.; Neft, R.E.; Belinsky, S.A. [and others

    1995-12-01

    New Mexico was the largest producer of uranium in the western world during 1960s and 1970s. Investigators at the University of New Mexico School of Medicine`s Epidemiology and Cancer Control Program have been conducting epidemiological studies on uranium miners over the past 2 decades. Currently, this cohort includes more than 3600 men who had completed at least 1 y of underground work experience in New Mexico by December 31, 1976. These miners, who are now in their 5th through 7th decades, the age when lung cancer incidence is highest, are at high risk for developing this disease because they were exposed to high levels of radon progeny in the mines, and they also smoked tobacco. However, not all people comparably exposed develop lung cancer; in fact, the lifetime risk of lung cancer for the smoking uranium miners has been projected by epidemiological analyses to be no higher than 50%. Therefore, the identification of gene alterations in bronchial epithelium would be a valuable tool to ascertain which miners are at greatest risk for lung cancer. The underlying significance of the current effort confirms the hypothesis that chronic exposure to high concentrations of {alpha}-particles and tobacco smoke produces genetically altered lung epithelial cells throughout the respiratory tract of some susceptible individuals before they develop clinical disease.

  7. Evaluation of prenatal screening for fetal chromosomal aneuploidies by non-invasive fetal cell-free DNA test%无创胎儿游离DNA检测技术在产前胎儿非整倍体筛查中的应用评价

    Institute of Scientific and Technical Information of China (English)

    穆煜; 王庆; 孙芾; 王厚芳; 常玲; Afnan Masoud; 唐莹

    2014-01-01

    Objective To evaluate the specificity and sensitivity of non-invasive fetal trisomy test (NIFTY) and study the prospects and feasibility of detected fetal DNA in maternal blood for prenatal screening of fetal chromosomal a-neuploidies. Methods NIFTY utilizes new generation high-throughput massively parallel DNA sequencing technologies to quantitatively analyze fetal cell-free DNA circulating in maternal plasma. According to the altered concentration of DNA to estimate the fetal chromosome numbers. Results From Mar, 2012 to May, 2013, 233 pregnant women in total were de-tected whose gestational ages ranged from 12~24 weeks. All of them had the pregnancies terminated by normal delivery or early terminations due to abnormal fetus. Eleven high risk pregnancies were detected during this period. In these high risk cases, 5 were Trisomy 21, 3 were Trisomy 18, 1 was Trisomy 13 and 2 were sexual chromosome X0. All NIFTY screened high risk cases were confirmed by cytogenetic tests. The specificity of the test was 100%. 222 were low risk for abnormal chromosome and no abnormal baby was found after birth, therefore, the test sensitivity was 100%. Conclusion Maternal peripheral blood fetal cfDNA test is a very good test method to detect fetal chromosomal aneuploidies. Comparing to the first and second trimester maternal serology screen tests, fetal cfDNA tests are reliable, sensitive with high accuracy. As a non-invasive test, it has no damage to pregnant women and no harm to the fetus.%目的:探讨无创胎儿染色体非整倍体检测技术(non-invasive fetal trisomy test, NIFTY)在胎儿染色体非整倍体产前筛查应用中的特异性和灵敏度。方法利用新一代高通量并行测序技术对母体外周血中的胎儿游离DNA(cell-free DNA, cfDNA)进行定量分析,根据相应DNA含量的变化推断胎儿染色体的异常状况。结果2012年3月至2013年5月,检测孕12~24周的孕妇外周血标本,对233份已结束妊娠的孕妇数

  8. Meiotic recombination, synapsis, meiotic inactivation and sperm aneuploidy in a chromosome 1 inversion carrier.

    Science.gov (United States)

    Kirkpatrick, Gordon; Chow, Victor; Ma, Sai

    2012-01-01

    Disrupted meiotic behaviour of inversion carriers may be responsible for suboptimal sperm parameters in these carriers. This study investigated meiotic recombination, synapsis, transcriptional silencing and chromosome segregation effects in a pericentric inv(1) carrier. Recombination (MLH1), synapsis (SYCP1, SYCP3) and transcriptional inactivation (γH2AX, BRCA1) were examined by fluorescence immunostaining. Chromosome specific rates of recombination were determined by fluorescence in-situ hybridization. Furthermore, testicular sperm was examined for aneuploidy and segregation of the inv(1). Our findings showed that global recombination rates were similar to controls. Recombination on the inv(1) and the sex chromosomes were reduced. The inv(1) associated with the XY body in 43.4% of cells, in which XY recombination was disproportionately absent, and 94.3% of cells displayed asynapsed regions which displayed meiotic silencing regardless of their association with the XY body. Furthermore, a low frequency of chromosomal imbalance was observed in spermatozoa (3.4%). Our results suggest that certain inversion carriers may display unimpaired global recombination and impaired recombination on the involved and the sex chromosomes during meiosis. Asynapsis or inversion-loop formation in the inverted region may be responsible for impaired spermatogenesis and may prevent sperm-chromosome imbalance.

  9. Peloruside A, a microtubule-stabilizing agent, induces aneuploidy in ovarian cancer cells.

    Science.gov (United States)

    Chan, Ariane; Singh, A Jonathan; Northcote, Peter T; Miller, John H

    2016-08-01

    To ensure proper chromosome segregation, mitosis is tightly regulated by the spindle assembly checkpoint (SAC). Low concentrations of microtubule-stabilizing agents can induce aneuploid populations of cells in the absence of G2/M block, suggesting pertubation of the spindle checkpoint. We investigated the effects of peloruside A, a microtubule-stabilizing agent, on expression levels of several key cell cycle proteins, MAD2, BUBR1, p55CDC and cyclin B1. Synchronized 1A9 ovarian carcinoma cells were allowed to progress through the cell cycle in the presence or absence of peloruside A. Co-immunoprecipitation and Western blotting were used to probe the cell cycle kinetics of MAD2 and BUBR1 dissociation from p55CDC. Using confocal microscopy, we investigated whether premature dissociation of MAD2 and BUBR1 at low (40 nM) but not high (100 nM) concentrations of peloruside A was caused by defects in the attachment of chromosomes to the mitotic spindle. An increased frequency of polar chromosomes was observed at low concentrations of peloruside A, suggesting that an increased frequency of pseudo-metaphase cells, which are not detected by the spindle assembly checkpoint, may be underlying the induction of aneuploidy. PMID:27155614

  10. Non-invasive prenatal testing for aneuploidy: current status and future prospects.

    Science.gov (United States)

    Benn, P; Cuckle, H; Pergament, E

    2013-07-01

    Non-invasive prenatal testing (NIPT) for aneuploidy using cell-free DNA in maternal plasma is revolutionizing prenatal screening and diagnosis. We review NIPT in the context of established screening and invasive technologies, the range of cytogenetic abnormalities detectable, cost, counseling and ethical issues. Current NIPT approaches involve whole-genome sequencing, targeted sequencing and assessment of single nucleotide polymorphism (SNP) differences between mother and fetus. Clinical trials have demonstrated the efficacy of NIPT for Down and Edwards syndromes, and possibly Patau syndrome, in high-risk women. Universal NIPT is not cost-effective, but using NIPT contingently in women found at moderate or high risk by conventional screening is cost-effective. Positive NIPT results must be confirmed using invasive techniques. Established screening, fetal ultrasound and invasive procedures with microarray testing allow the detection of a broad range of additional abnormalities not yet detectable by NIPT. NIPT approaches that take advantage of SNP information potentially allow the identification of parent of origin for imbalances, triploidy, uniparental disomy and consanguinity, and separate evaluation of dizygotic twins. Fetal fraction enrichment, improved sequencing and selected analysis of the most informative sequences should result in tests for additional chromosomal abnormalities. Providing adequate prenatal counseling poses a substantial challenge given the broad range of prenatal testing options now available. PMID:23765643

  11. Prospective evaluation of first trimester combined screening for trisomy 21 using a double set of the maternal serum markers PAPP-A and free β-hCG

    DEFF Research Database (Denmark)

    Ekelund, Charlotte Kvist; Wright, Dave; Ball, Susan;

    Objective: To prospectively evaluate the screening performance of first trimester combined screening for trisomy 21 using a double set of biochemical markers Methods: Three fetal medicine departments in Denmark participated in the study. Screening for trisomy 21 was set up as a two-step approach...... with an early blood sample taken prior to the NT scan, and another blood sample taken at the time of the NT scan. PAPP-A and free β-hCG were measured on both the early and the late samples, and Multiples of the Median (MoM) values were calculated in addition to the corresponding trisomy 21 risk. Using...... statistical modelling we estimated detection rates (DR) and false positive rates (FPR) when using early sampling, late sampling or combinations of early and late sampling. Results: We collected two blood samples in 25 pregnancies affected by trisomy 21 and in 3942 control pregnancies. The early samples were...

  12. Women's Experiences and Preferences for Service Delivery of Non-Invasive Prenatal Testing for Aneuploidy in a Public Health Setting: A Mixed Methods Study.

    Directory of Open Access Journals (Sweden)

    Celine Lewis

    Full Text Available Non-invasive prenatal testing (NIPT for aneuploidy is currently only available in the UK through the private sector outside of the research arena. As part of an implementation study in the UK National Health Service we conducted a mixed methods study to assess women's experience of being offered NIPT using validated measures of decisional conflict, decisional regret and anxiety. Clinical service preferences were also explored. Women with a Down syndrome screening risk >1:1000 were invited to take part in the study and offered NIPT, NIPT and invasive testing (for women with a risk above 1:150 or no further testing. A cross-sectional survey and semi-structured interviews were conducted at two time points; at the time of testing and one month following receipt of results (or equivalent for NIPT decliners. In total, 845 questionnaires and 81 interviews were analysed. The main motivation to accept NIPT was for reassurance (30.8%. Decisional conflict occurred in a minimal number of cases (3.8%, however, none of the participants experienced decisional regret. Around a third (29.9% of women had elevated anxiety at the time of testing, including intermediate risk women who traditionally would not be offered further testing (54.4% high risk; 20.1% medium risk, a finding supported through the qualitative interviews where prolonged or additional anxiety was found to occur in some medium risk cases. Women were overwhelmingly positive about the opportunity to have a test that was procedurally safe, accurate, reduced the need for invasive testing and identified cases of Down syndrome that might otherwise have been missed. Reassurance was identified as the main motivator for accepting NIPT, particularly amongst medium risk women, with high risk women inclined to accept NIPT to inform decisions around invasive testing. The current turnaround time for test result was identified as a key limitation. All the women interviewed thought NIPT should be adopted as part

  13. Women’s Experiences and Preferences for Service Delivery of Non-Invasive Prenatal Testing for Aneuploidy in a Public Health Setting: A Mixed Methods Study

    Science.gov (United States)

    Lewis, Celine; Hill, Melissa; Chitty, Lyn S.

    2016-01-01

    Non-invasive prenatal testing (NIPT) for aneuploidy is currently only available in the UK through the private sector outside of the research arena. As part of an implementation study in the UK National Health Service we conducted a mixed methods study to assess women’s experience of being offered NIPT using validated measures of decisional conflict, decisional regret and anxiety. Clinical service preferences were also explored. Women with a Down syndrome screening risk >1:1000 were invited to take part in the study and offered NIPT, NIPT and invasive testing (for women with a risk above 1:150) or no further testing. A cross-sectional survey and semi-structured interviews were conducted at two time points; at the time of testing and one month following receipt of results (or equivalent for NIPT decliners). In total, 845 questionnaires and 81 interviews were analysed. The main motivation to accept NIPT was for reassurance (30.8%). Decisional conflict occurred in a minimal number of cases (3.8%), however, none of the participants experienced decisional regret. Around a third (29.9%) of women had elevated anxiety at the time of testing, including intermediate risk women who traditionally would not be offered further testing (54.4% high risk; 20.1% medium risk), a finding supported through the qualitative interviews where prolonged or additional anxiety was found to occur in some medium risk cases. Women were overwhelmingly positive about the opportunity to have a test that was procedurally safe, accurate, reduced the need for invasive testing and identified cases of Down syndrome that might otherwise have been missed. Reassurance was identified as the main motivator for accepting NIPT, particularly amongst medium risk women, with high risk women inclined to accept NIPT to inform decisions around invasive testing. The current turnaround time for test result was identified as a key limitation. All the women interviewed thought NIPT should be adopted as part of NHS

  14. CD34 cells from patients with trisomy 8 myelodysplastic syndrome (MDS) express early apoptotic markers but avoid programmed cell death by up-regulation of antiapoptotic proteins

    OpenAIRE

    Sloand, Elaine M.; Pfannes, Loretta; Chen, Gubin; Shah, Simant; Solomou, Elena E.; Barrett, John; Neal S Young

    2007-01-01

    CD34 cells from patients with trisomy 8 myelodysplastic syndrome (MDS) are distinguished from other MDS cells and from normal hematopoietic cells by their pronounced expression of apoptotic markers. Paradoxically, trisomy 8 clones can persist in patients with bone marrow failure and expand following immunosuppression. We previously demonstrated up-regulation of c-myc and CD1 by microarray analysis. Here, we confirmed these findings by real-time polymerase chain reaction (PCR), demonstrated up...

  15. GATA1 mutation negative acute megakaryoblastic leukemia with acquired trisomy 21 presenting with extensive bone marrow necrosis in an adult: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Todd P. Williams

    2016-03-01

    Conclusions: To our knowledge, this is the first reported case of an adult with AMKL with acquired trisomy 21 in which the GATA1 mutation was investigated and the second reported case of AMKL presenting with extensive bone marrow necrosis. We will present a diagnostic approach to AMKL in which extensive bone marrow necrosis renders examination of the bone marrow difficult. Furthermore, we will examine the absence of the GATA1 mutation in a case of AMKL with trisomy 21 in an adult.

  16. Cerebral cortical astroglia from the trisomy 16 mouse, a model for Down syndrome, produce neuronal cholinergic deficits in cell culture

    OpenAIRE

    Nelson, P. G.; Fitzgerald, S.; Rapoport, S I; Neale, E A; Galdzicki, Z; Dunlap, V.; Bowers, L; v. Agoston, D.

    1997-01-01

    Trisomy 21 (Down syndrome) is associated with a high incidence of Alzheimer disease and with deficits in cholinergic function in humans. We used the trisomy 16 (Ts16) mouse model for Down syndrome to identify the cellular basis for the cholinergic dysfunction. Cholinergic neurons and cerebral cortical astroglia, obtained separately from Ts16 mouse fetuses and their euploid littermates, were cultured in various combinations. Choline acetyltransferase activity and cholinergic neuron number were...

  17. Cancer quasispecies and stem-like adaptive aneuploidy [v1; ref status: indexed, http://f1000r.es/29s

    Directory of Open Access Journals (Sweden)

    Domenico Napoletani

    2013-12-01

    Full Text Available In this paper we develop a theoretical frame to understand self-regulation of aneuploidy rate in cancer and stem cells. This is accomplished building upon quasispecies theory, by leaving its formal mathematical structure intact, but by drastically changing the meaning of its objects. In particular, we propose a novel definition of chromosomal master sequence, as a sequence of physically distinct whole or fragmented chromosomes, whose length is taken to be the sum of the copy numbers of each whole or fragmented chromosome. This fundamental change in the functional objects of quasispecies theory allows us to show that previously measured aneuploidy rates in cancer populations are already close to a formally derived aneuploid error threshold, and that any value of aneuploidy rate larger than the aneuploid error threshold would lead to a loss of fitness of a tumor population. Finally, we make a phenomenological analysis of existing experimental evidence to argue that single clone cancer cells, derived from an aneuploid cancer subpopulation, are capable of self-regulating their aneuploidy rate and of adapting it to distinct environments, namely primary and metastatic microenvironments. We also discuss the potential origin of this self-regulatory ability in the wider context of developmental and comparative biology and we hypothesize the existence of a diversification factor, i.e. a cellular mechanism that regulates adaptation of aneuploidy rates, active in all embryo, adult and cancer stem cells.

  18. A Syntenic Cross Species Aneuploidy Genetic Screen Links RCAN1 Expression to β-Cell Mitochondrial Dysfunction in Type 2 Diabetes

    Science.gov (United States)

    Peiris, Heshan; Duffield, Michael D.; Fadista, Joao; Kashmir, Vinder; Genders, Amanda J.; McGee, Sean L.; Martin, Alyce M.; Saiedi, Madiha; Morton, Nicholas; Carter, Roderick; Cousin, Michael A.; Oskolkov, Nikolay; Volkov, Petr; Hough, Tertius A.; Fisher, Elizabeth M. C.; Tybulewicz, Victor L. J.; Busciglio, Jorge; Coskun, Pinar E.; Becker, Ann; Belichenko, Pavel V.; Mobley, William C.; Ryan, Michael T.; Chan, Jeng Yie; Laybutt, D. Ross; Coates, P. Toby; Yang, Sijun; Ling, Charlotte; Groop, Leif; Pritchard, Melanie A.; Keating, Damien J.

    2016-01-01

    Type 2 diabetes (T2D) is a complex metabolic disease associated with obesity, insulin resistance and hypoinsulinemia due to pancreatic β-cell dysfunction. Reduced mitochondrial function is thought to be central to β-cell dysfunction. Mitochondrial dysfunction and reduced insulin secretion are also observed in β-cells of humans with the most common human genetic disorder, Down syndrome (DS, Trisomy 21). To identify regions of chromosome 21 that may be associated with perturbed glucose homeostasis we profiled the glycaemic status of different DS mouse models. The Ts65Dn and Dp16 DS mouse lines were hyperglycemic, while Tc1 and Ts1Rhr mice were not, providing us with a region of chromosome 21 containing genes that cause hyperglycemia. We then examined whether any of these genes were upregulated in a set of ~5,000 gene expression changes we had identified in a large gene expression analysis of human T2D β-cells. This approach produced a single gene, RCAN1, as a candidate gene linking hyperglycemia and functional changes in T2D β-cells. Further investigations demonstrated that RCAN1 methylation is reduced in human T2D islets at multiple sites, correlating with increased expression. RCAN1 protein expression was also increased in db/db mouse islets and in human and mouse islets exposed to high glucose. Mice overexpressing RCAN1 had reduced in vivo glucose-stimulated insulin secretion and their β-cells displayed mitochondrial dysfunction including hyperpolarised membrane potential, reduced oxidative phosphorylation and low ATP production. This lack of β-cell ATP had functional consequences by negatively affecting both glucose-stimulated membrane depolarisation and ATP-dependent insulin granule exocytosis. Thus, from amongst the myriad of gene expression changes occurring in T2D β-cells where we had little knowledge of which changes cause β-cell dysfunction, we applied a trisomy 21 screening approach which linked RCAN1 to β-cell mitochondrial dysfunction in T2D

  19. A Syntenic Cross Species Aneuploidy Genetic Screen Links RCAN1 Expression to β-Cell Mitochondrial Dysfunction in Type 2 Diabetes.

    Directory of Open Access Journals (Sweden)

    Heshan Peiris

    2016-05-01

    Full Text Available Type 2 diabetes (T2D is a complex metabolic disease associated with obesity, insulin resistance and hypoinsulinemia due to pancreatic β-cell dysfunction. Reduced mitochondrial function is thought to be central to β-cell dysfunction. Mitochondrial dysfunction and reduced insulin secretion are also observed in β-cells of humans with the most common human genetic disorder, Down syndrome (DS, Trisomy 21. To identify regions of chromosome 21 that may be associated with perturbed glucose homeostasis we profiled the glycaemic status of different DS mouse models. The Ts65Dn and Dp16 DS mouse lines were hyperglycemic, while Tc1 and Ts1Rhr mice were not, providing us with a region of chromosome 21 containing genes that cause hyperglycemia. We then examined whether any of these genes were upregulated in a set of ~5,000 gene expression changes we had identified in a large gene expression analysis of human T2D β-cells. This approach produced a single gene, RCAN1, as a candidate gene linking hyperglycemia and functional changes in T2D β-cells. Further investigations demonstrated that RCAN1 methylation is reduced in human T2D islets at multiple sites, correlating with increased expression. RCAN1 protein expression was also increased in db/db mouse islets and in human and mouse islets exposed to high glucose. Mice overexpressing RCAN1 had reduced in vivo glucose-stimulated insulin secretion and their β-cells displayed mitochondrial dysfunction including hyperpolarised membrane potential, reduced oxidative phosphorylation and low ATP production. This lack of β-cell ATP had functional consequences by negatively affecting both glucose-stimulated membrane depolarisation and ATP-dependent insulin granule exocytosis. Thus, from amongst the myriad of gene expression changes occurring in T2D β-cells where we had little knowledge of which changes cause β-cell dysfunction, we applied a trisomy 21 screening approach which linked RCAN1 to β-cell mitochondrial

  20. A Syntenic Cross Species Aneuploidy Genetic Screen Links RCAN1 Expression to β-Cell Mitochondrial Dysfunction in Type 2 Diabetes.

    Science.gov (United States)

    Peiris, Heshan; Duffield, Michael D; Fadista, Joao; Jessup, Claire F; Kashmir, Vinder; Genders, Amanda J; McGee, Sean L; Martin, Alyce M; Saiedi, Madiha; Morton, Nicholas; Carter, Roderick; Cousin, Michael A; Kokotos, Alexandros C; Oskolkov, Nikolay; Volkov, Petr; Hough, Tertius A; Fisher, Elizabeth M C; Tybulewicz, Victor L J; Busciglio, Jorge; Coskun, Pinar E; Becker, Ann; Belichenko, Pavel V; Mobley, William C; Ryan, Michael T; Chan, Jeng Yie; Laybutt, D Ross; Coates, P Toby; Yang, Sijun; Ling, Charlotte; Groop, Leif; Pritchard, Melanie A; Keating, Damien J

    2016-05-01

    Type 2 diabetes (T2D) is a complex metabolic disease associated with obesity, insulin resistance and hypoinsulinemia due to pancreatic β-cell dysfunction. Reduced mitochondrial function is thought to be central to β-cell dysfunction. Mitochondrial dysfunction and reduced insulin secretion are also observed in β-cells of humans with the most common human genetic disorder, Down syndrome (DS, Trisomy 21). To identify regions of chromosome 21 that may be associated with perturbed glucose homeostasis we profiled the glycaemic status of different DS mouse models. The Ts65Dn and Dp16 DS mouse lines were hyperglycemic, while Tc1 and Ts1Rhr mice were not, providing us with a region of chromosome 21 containing genes that cause hyperglycemia. We then examined whether any of these genes were upregulated in a set of ~5,000 gene expression changes we had identified in a large gene expression analysis of human T2D β-cells. This approach produced a single gene, RCAN1, as a candidate gene linking hyperglycemia and functional changes in T2D β-cells. Further investigations demonstrated that RCAN1 methylation is reduced in human T2D islets at multiple sites, correlating with increased expression. RCAN1 protein expression was also increased in db/db mouse islets and in human and mouse islets exposed to high glucose. Mice overexpressing RCAN1 had reduced in vivo glucose-stimulated insulin secretion and their β-cells displayed mitochondrial dysfunction including hyperpolarised membrane potential, reduced oxidative phosphorylation and low ATP production. This lack of β-cell ATP had functional consequences by negatively affecting both glucose-stimulated membrane depolarisation and ATP-dependent insulin granule exocytosis. Thus, from amongst the myriad of gene expression changes occurring in T2D β-cells where we had little knowledge of which changes cause β-cell dysfunction, we applied a trisomy 21 screening approach which linked RCAN1 to β-cell mitochondrial dysfunction in T2D.

  1. A Syntenic Cross Species Aneuploidy Genetic Screen Links RCAN1 Expression to β-Cell Mitochondrial Dysfunction in Type 2 Diabetes.

    Science.gov (United States)

    Peiris, Heshan; Duffield, Michael D; Fadista, Joao; Jessup, Claire F; Kashmir, Vinder; Genders, Amanda J; McGee, Sean L; Martin, Alyce M; Saiedi, Madiha; Morton, Nicholas; Carter, Roderick; Cousin, Michael A; Kokotos, Alexandros C; Oskolkov, Nikolay; Volkov, Petr; Hough, Tertius A; Fisher, Elizabeth M C; Tybulewicz, Victor L J; Busciglio, Jorge; Coskun, Pinar E; Becker, Ann; Belichenko, Pavel V; Mobley, William C; Ryan, Michael T; Chan, Jeng Yie; Laybutt, D Ross; Coates, P Toby; Yang, Sijun; Ling, Charlotte; Groop, Leif; Pritchard, Melanie A; Keating, Damien J

    2016-05-01

    Type 2 diabetes (T2D) is a complex metabolic disease associated with obesity, insulin resistance and hypoinsulinemia due to pancreatic β-cell dysfunction. Reduced mitochondrial function is thought to be central to β-cell dysfunction. Mitochondrial dysfunction and reduced insulin secretion are also observed in β-cells of humans with the most common human genetic disorder, Down syndrome (DS, Trisomy 21). To identify regions of chromosome 21 that may be associated with perturbed glucose homeostasis we profiled the glycaemic status of different DS mouse models. The Ts65Dn and Dp16 DS mouse lines were hyperglycemic, while Tc1 and Ts1Rhr mice were not, providing us with a region of chromosome 21 containing genes that cause hyperglycemia. We then examined whether any of these genes were upregulated in a set of ~5,000 gene expression changes we had identified in a large gene expression analysis of human T2D β-cells. This approach produced a single gene, RCAN1, as a candidate gene linking hyperglycemia and functional changes in T2D β-cells. Further investigations demonstrated that RCAN1 methylation is reduced in human T2D islets at multiple sites, correlating with increased expression. RCAN1 protein expression was also increased in db/db mouse islets and in human and mouse islets exposed to high glucose. Mice overexpressing RCAN1 had reduced in vivo glucose-stimulated insulin secretion and their β-cells displayed mitochondrial dysfunction including hyperpolarised membrane potential, reduced oxidative phosphorylation and low ATP production. This lack of β-cell ATP had functional consequences by negatively affecting both glucose-stimulated membrane depolarisation and ATP-dependent insulin granule exocytosis. Thus, from amongst the myriad of gene expression changes occurring in T2D β-cells where we had little knowledge of which changes cause β-cell dysfunction, we applied a trisomy 21 screening approach which linked RCAN1 to β-cell mitochondrial dysfunction in T2D

  2. Cystic Dilation of the Aqueductus Sylvii in Case of Trisomy 17p11.2—pter with the Deletion of the Terminal Portion of the Chromosome 6

    Directory of Open Access Journals (Sweden)

    Emese Horváth

    2010-01-01

    Full Text Available Since the 1970s, about 30 cases of partial or complete trisomy 17p have been presented in the literature. Partial trisomies of the short arm of chromosome 17 are somewhat more common, but complete trisomy is quite rare. Most of these cases were described in infants and newborns; and to our knowledge only 3 cases of trisomy 17p have been detected intrauterine. Phenotypic features of trisomy 17p in fetuses are intrauterine growth retardation, ventriculomegaly, cleft lip and cleft palate, micrognathia, horseshoe kidneys, single umbilical artery, and congenital heart defects. The sonographic and foetopathologic findings of a pregnancy trisomy 17p11.2—pter with the deletion of the terminal portion of the chromosome 6 due to paternal balanced translocation are described in this case report.

  3. Trissomia do cromossomo 9 associada com aumento da translucência nucal: correlação ultra-sonográfica e anatomopatológica ¾ relato de um caso Trisomy 9 with increased nuchal translucency: ultrasound and pathologic correlation - a case report

    Directory of Open Access Journals (Sweden)

    Carlos Geraldo Viana Murta

    2001-04-01

    Full Text Available Relatamos um caso de trissomia completa do cromossomo 9 associada com aumento da translucência nucal (9,1 mm, diagnosticada por ultra-som na 12ª semana de gestação e confirmada por cariótipo em espécime de biópsia do vilo corial. Múltiplas anomalias congênitas foram diagnosticadas no exame ultra-sonográfico e confirmadas na autópsia. Embora rara, a trissomia 9 deve ser incluída no rol das anomalias cromossômicas associadas com aumento da translucência nucal.We report a case of prenatal diagnosis of trisomy 9 in a fetus presenting increased translucency thickness (9.1 mm observed on an ultrasound scan performed at 12 weeks pregnancy and confirmed by cariotype analysis of biopsy material obtained from the chorionic villi. Multiple trisomy 9 characteristic abnormalities were detected by ultrasound and confirmed by autopsy and histopathological examination. Although rare, trisomy 9 should be included in the list of chromosomic anomalies associated with increased translucency.

  4. 产前超声指标评分法对胎儿18三体综合征的诊断价值%Prenatal diagnosis of trisomy 18 syndrome with sonogram index scoring system

    Institute of Scientific and Technical Information of China (English)

    彭软; 谢红宁; 张颖; 罗艳敏; 李丽娟; 朱云晓; 林美芳

    2011-01-01

    各分值的敏感度和特异度,ROC曲线下面积为0.999.以总评分4分为最佳诊断值,诊断18三体征的敏感度为0.966,特异度为0.997.结论 超声指标评分法对18三体综合征具有较好的诊断价值,以4分作为诊断18三体综合征截断值其诊断效价最高.%Objective To explore the value of sonogram index scoring system in the prenatal diagnosis of trisomy 18 syndrome.Methods Neonates who had prenatal sonographic screening in our tertiary center were followed up from January 2004 to December 2009.The fetuses who were suspected with abnormalities received karyotype analysis.All fetuses were divided into case group ( trisomy 18 group) and the control group (non-trisomy 18 group).The latter group was constituted of fetuses with trisomy 21,trisomy 13,other chromosomal abnormalitis and fetuses with normal karyotype.Logistic regression analysis was done to decide the individual sonographic features of trisomy 18.A score was assigned for ultrasound markers according to their likelihood ratios for trisomy 18 syndrome.A score of 3 was assigned for the sonographic features with likelihood ratio over 200,2 for those with likelihood ratio between 100 and 200,and 1 for those with likelihood ratio less than 100.The diagnostic efficacy of the ultrasound index scoring system was evaluated by diagnostic test.The optimal cutoff value was determined by receiver operating characteristic (ROC) curve.Results The study group included 59 fetuses with trisomy 18.And 26 486 fetuses did not have trisomy 18 syndrome,including 93 fetuses with trismoy 21,19 fetuses with trisomy 13,134 fetuses with other chromosomal abnormalities,3739 fetuses with normal karyotype and 22 501 fetuses with normal appearance after birth.Two or more structural defects were observed in each trisomy 18 fetus.The highest incidence of sonogram abnormalities was extremities abnormalities (85%,50/59 ),followed by cardiac defects (83%,49/59) and central nervous system (CNS

  5. Analysis of Prenatal diagnosis results of trisomy 18 fetus%18-三体综合征胎儿的产前诊断结果分析

    Institute of Scientific and Technical Information of China (English)

    韩瑾; 何平; 廖灿; 张蒙; 甄理; 杨昕; 潘敏; 李东至; 易翠兴; 袁思敏; 钟慧珠

    2016-01-01

    Objective To assess clinical application of prenatal diagnosis in trisomy 18 during pregnancy.Methods A total of 13 354 cases received invasive prenatal diagnosis at Prenatal Diagnosis Center,Guangzhou Woman and Children′s Medical Center between January 2010 and August 2014. Among them, 95 fetus were diagnosed as trisomy 18.Three prenatal diagnostic methods included chorionic villi biopsy (1 1-13 +6 gestational weeks),amniocentesis (1 6-24 gestational weeks)and percutaneous puncture of umbilical cord (> 24 gestational weeks).The indications of prenatal diagnosis, abnormal karyotype of chromosome of fetus, and ultrasonic abnormal manifestations of 95 cases with trisomy 18 were analyzed.The study protocol was approved by the Ethical Review Board of Investigation in Human Being of Guangzhou Woman and Children′s Medical Center.Informed consent was obtained from each participates.Results ① Indications:46 cases (48.5%)of 95 cases were high risk in the first trimester screening,47 cases (48.4%)were high risk in the second and third trimester,the remaining 2 cases of indications were high risk in non-invasive prenatal test (NIPT)and carriers ofα-thalassemia.Furthermore,among 95 cases with trisomy 18,33 pregnant women underwent chorionic villi biopsy, 46 underwent amniocentesis, and other 1 6 underwent percutaneous puncture of umbrlical cord.② Chromosome karyotypes:except of 91 cases (95.8%)simple karyotype of trisomy 18,4 cases (4.2%)were chromosome mosaic.Among them, 2 cases of mosaic ratio than 20% were found structure abnormalities in the first trimester screening. One in 1 1.0% was high risk in the second trimester screening.One in 8.0% had no findings in the first and second trimester screening,while had fetal growth restriction (FGR)in the third trimester.③ The main ultrasound findings in the first trimester of 38 cases (82.6%)were nuchal translucency (NT)thickening,nasal bone absence or hypoplasia,cystic hygroma,omphalocele and anencephaly, another 40

  6. Mechanisms involved in the induction of aneuploidy: the significance of chromosome loss

    Directory of Open Access Journals (Sweden)

    A.I. Seoane

    2000-12-01

    Full Text Available The induction of aneuploidy by physical and chemical agents using different test systems was evaluated. The effect of X-rays, caffeine, acetaldehyde, ethanol, diethylstilbestrol, propionaldehyde, and chloral hydrate was studied by chromosome counting in Chinese hamster embryonic diploid cells. Aneugenic ability of cadmium chloride, cadmium sulfate, potassium dichromate, chromium chloride, nickel chloride, and nickel sulfate was assessed by means of anaphase-telophase analysis in Chinese hamster ovary cells. Chromosome counting in human fibroblasts (MRC-5 cell line was employed to evaluate the effect of cacodilic acid, cadmium chloride, cadmium sulfate, and potassium dichromate. Finally, the induction of kinetochore-positive and kinetochore negative micronuclei by cadmium chloride, cadmium sulfate, potassium dichromate, chromium chloride, and nickel chloride was studied using CREST antibodies. When the effect of different agents was determined by chromosome counting, an increase of hypoploid but not of hyperploid cells was observed. Anaphase-telophase analysis showed that metal salts increased the frequency of lagging chromosomes. This finding has been confirmed by the increment of kinetochore-positive micronuclei using CREST antibodies. Therefore, chromosome loss could be considered as the main cause of induced aneuploidy.A indução de aneuploidia por agentes físicos e químicos usando diferentes sistemas de teste foi avaliada. O efeito de raios-X, cafeína, acetaldeído, etanol, dietilestilbestrol, propionaldeído e hidrato de cloral foi estudado por contagem cromossômica em células diplóides embriônicas de hamster chinês. A habilidade aneugênica de cloreto de cádmio, sulfato de cádmio, dicromato de potássio, cloreto de crômio, cloreto de níquel e sulfato de níquel foi avaliada por meio de análise de anáfase-telófase em células de ovário de hamster chinês. A contagem cromossômica em fibroblastos humanos (linhagem celular

  7. Constellation of congenital abnormalities in an infant: A new syndrome or tissue-specific mosaicism for trisomy 18?

    Energy Technology Data Exchange (ETDEWEB)

    Shashi, V.; Golden, W.L.; von Kap-Herr, C.; Wilson, W.G. [Univ. of Virginia Health Sciences Center, Charlottesville (United States)

    1996-03-01

    A newborn infant born to consanguineous (first cousin) parents was noted to have complex cogenital heart defect and minor anomalies suggestive of trisomy 18. Blood lymphocyte and skin fibroblast karyotypes were normal. He died in the neonatal period of postoperative complications. On interphase fluorescence in-situ hybridization (FISH) using autopsy specimens, a significant number of cells in the liver (17%) were trisomic for chromosome 18, compared to normal control liver tissue. However, interphase FISH analyses of blood lymphocytes, skin fibroblasts, and kidney tissue were normal. It is our opinion that this apparent mosaicism for trisomy 18 in the patient`s liver may be spurious, though it brings into focus the issue of possible tissue/organ-specific mosaicism. The anomalies in this infant do not resemble a previously described malformation syndrome. Parental consanguinity raises the possibility that this represents a new autosomal recessive malformation syndrome. 15 refs., 3 figs., 3 tabs.

  8. Prenatal detection of aneuploidies using fluorescence in situ hybridization: A preliminary experience in an Indian set up

    Indian Academy of Sciences (India)

    Vaidehi Jobanputra; Kalol Kumar Roy; Kiran Kucheria

    2002-03-01

    Fluorescence in situ hybridization (FISH) is a powerful molecular cytogenetic technique which allows rapid detection of aneuploidies on interphase cells and metaphase spreads. The aim of the present study was to evaluate FISH as a tool in prenatal diagnosis of aneuploidies in high risk pregnancies in an Indian set up. Prenatal diagnosis was carried out in 88 high-risk pregnancies using FISH and cytogenetic analysis. Multicolour commercially available FISH probes specific for chromosomes 13, 18, 21, X and Y were used. Interphase FISH was done on uncultured cells from chorionic villus and amniotic fluid samples. FISH on metaphase spreads was done from cord blood samples. The results of FISH were in conformity with the results of cytogenetic analysis in all the normal and aneuploid cases except in one case of structural chromosomal abnormality. The hybridization efficiency of the 5 probes used for the detection of aneuploidies was 100%. Using these probes FISH assay yielded discrete differences in the signal profiles between cytogenetically normal and abnormal samples. The overall mean interphase disomic signal patterns of chromosomes 13, 18, 21, X and Y were 94.45%; for interphase trisomic signal pattern of chromosome 21 was 97.3%. Interphase FISH is very useful in urgent high risk cases. The use of FISH overcomes the difficulties of conventional banding on metaphase spreads and reduces the time of reporting. However, with the limited number of probes used, the conventional cytogenetic analysis serves as a gold standard at present. It should be employed as an adjunctive tool to conventional cytogenetics.

  9. RNAi mediated acute depletion of Retinoblastoma protein (pRb promotes aneuploidy in human primary cells via micronuclei formation

    Directory of Open Access Journals (Sweden)

    Iovino Flora

    2009-11-01

    Full Text Available Abstract Background Changes in chromosome number or structure as well as supernumerary centrosomes and multipolar mitoses are commonly observed in human tumors. Thus, centrosome amplification and mitotic checkpoint dysfunctions are believed possible causes of chromosomal instability. The Retinoblastoma tumor suppressor (RB participates in the regulation of synchrony between DNA synthesis and centrosome duplication and it is involved in transcription regulation of some mitotic genes. Primary human fibroblasts were transfected transiently with short interfering RNA (siRNA specific for human pRb to investigate the effects of pRb acute loss on chromosomal stability. Results Acutely pRb-depleted fibroblasts showed altered expression of genes necessary for cell cycle progression, centrosome homeostasis, kinetochore and mitotic checkpoint proteins. Despite altered expression of genes involved in the Spindle Assembly Checkpoint (SAC the checkpoint seemed to function properly in pRb-depleted fibroblasts. In particular AURORA-A and PLK1 overexpression suggested that these two genes might have a role in the observed genomic instability. However, when they were post-transcriptionally silenced in pRb-depleted fibroblasts we did not observe reduction in the number of aneuploid cells. This finding suggests that overexpression of these two genes did not contribute to genomic instability triggered by RB acute loss although it affected cell proliferation. Acutely pRb-depleted human fibroblasts showed the presence of micronuclei containing whole chromosomes besides the presence of supernumerary centrosomes and aneuploidy. Conclusion Here we show for the first time that RB acute loss triggers centrosome amplification and aneuploidy in human primary fibroblasts. Altogether, our results suggest that pRb-depleted primary human fibroblasts possess an intact spindle checkpoint and that micronuclei, likely caused by mis-attached kinetochores that in turn trigger

  10. Non-invasive Prenatal Diagnosis of Chromosome Aneuploidy by Massively Parallel Genomic Sequencing Technology%大规模并行基因组测序技术应用于无创产前诊断染色体非整倍体的研究

    Institute of Scientific and Technical Information of China (English)

    李玉芝; 王威; 任景慧; 林琳华; 姚秋璇; 袁红; 郭辉; 李启运; 何薇; 张红云

    2012-01-01

    Objective To perform non-invasive prenatal diagnosis of chromosome aneuploidy by detecting free DNA in maternal peripheral plasma by using massively parallel genomic sequencing technology. Methods 941 older pregnant women with gestational age among 8 to 30 weeks were chosen ,who were registered in prenatal diagnostic centers of Shenzhen People 's Hospital from January 2009 to July 2010 ,had high-risk in Down syndrome biochemical screening and/or were shown fetal abnormalities by color Doppler ultrasound. The peripheral venous blood from the pregnant women was drawn ,plasma DNA was extracted,and the sequencing library was prepared. By using Illumina HiSeq2000 ,high-throughput sequencing procedure was carried out. The sequencing data were compared with the human reference gene-database and statistically analyzed. Simultaneously ,the cells isolated from the fetal amniotic fluid or umbilical cord blood were cultured ,and chromosomal karyotyping was done to I-dentify the chromosome aneuploidy. Results ①In 27 out of 941 pregnant women,massively parallel genomic sequencing technology revealed high-risk of Down syndrome. Using the results of chromosomal karyotype analysis of cells from amniotic fluid or umbilical cord blood as the gold standard ,2 from the 27 high-risk fetuses were misdiagnosed :one had karyotype of 47 ,XXY , and the other had normal karyotype. The detection rate of fetal Down syndrome was 100% (25/25)with accuracy rate being 99. 78% (939/941),and misdiagnosis rate being 0. 22% (2/941) ,②Of 941 samples,high-risk of 18-trisomy was detected in 14 cases. One 18-trisomy fetus was missed. Compared with karyotyping results ,non-invasive prenatal genetic detection rate of 18-trisomy fetus was 93. 33% (14/15),missed diagnosis rate was 6. 67% (1/15) ,and misdiagnosis rate was 0. Conclusion Massively parallel sequencing technology for noninvasive prenatal diagnosis of the fetus chromosome aneuploidy by detecting plasma free DNA in pregnant women ,which is highly

  11. Triangulating the sexually dimorphic brain through high-resolution neuroimaging of murine sex chromosome aneuploidies.

    Science.gov (United States)

    Raznahan, Armin; Lue, YanHe; Probst, Frank; Greenstein, Deanna; Giedd, Jay; Wang, Christina; Lerch, Jason; Swerdloff, Ronald

    2015-11-01

    Murine sex chromosome aneuploidies (SCAs) provide powerful models for charting sex chromosome influences on mammalian brain development. Here, building on prior work in X-monosomic (XO) mice, we use spatially non-biased high-resolution imaging to compare and contrast neuroanatomical alterations in XXY and XO mice relative to their wild-type XX and XY littermates. First, we show that carriage of a supernumerary X chromosome in XXY males (1) does not prevent normative volumetric masculinization of the bed nucleus of the stria terminalis (BNST) and medial amygdala, but (2) causes distributed anatomical alterations relative to XY males, which show a statistically unexpected tendency to be co-localized with and reciprocal to XO-XX differences in anatomy. These overlaps identify the lateral septum, BNST, ventral group thalamic nuclei and periaqueductal gray matter as regions with replicable sensitivity to X chromosome dose across two SCAs. We then harness anatomical variation across all four karyotype groups in our study--XO, XX, XY and XXY--to create an agnostic data-driven segmentation of the mouse brain into five distributed clusters which (1) recover fundamental properties of brain organization with high spatial precision, (2) define two previously uncharacterized systems of relative volume excess in females vs. males ("forebrain cholinergic" and "cerebelo-pontine-thalamo-cortical"), and (3) adopt stereotyped spatial motifs which delineate ordered gradients of sex chromosome and gonadal influences on volumetric brain development. Taken together, these data provide a new framework for the study of sexually dimorphic influences on brain development in health and disrupted brain development in SCA.

  12. Folic acid deficiency increases chromosomal instability, chromosome 21 aneuploidy and sensitivity to radiation-induced micronuclei

    International Nuclear Information System (INIS)

    Folic acid deficiency can lead to uracil incorporation into DNA, hypomethylation of DNA, inefficient DNA repair and increase chromosome malsegregation and breakage. Because ionising radiation increases demand for efficient DNA repair and also causes chromosome breaks we hypothesised that folic acid deficiency may increase sensitivity to radiation-induced chromosome breakage. We tested this hypothesis by using the cytokinesis-block micronucleus assay in 10 day WIL2-NS cell cultures at four different folic acid concentrations (0.2, 2, 20, and 200 nM) that span the 'normal' physiological range in humans. The study showed a significant dose-dependent increase in frequency of binucleated cells with micronuclei and/or nucleoplasmic bridges with decreasing folic acid concentration (P < 0.0001, P = 0.028, respectively). These biomarkers of chromosomal instability were also increased in cells irradiated (1.5 Gy γ-rays) on day 9 relative to un-irradiated controls (P < 0.05). Folic acid deficiency and γ-irradiation were shown to have a significant interactive effect on frequency of cells containing micronuclei (two-way ANOVA, interaction P 0.0039) such that the frequency of radiation-induced micronucleated cells (i.e. after subtracting base-line frequency of un-irradiated controls) increased with decreasing folic acid concentration (P-trend < 0.0001). Aneuploidy of chromosome 21, apoptosis and necrosis were increased by folic acid deficiency but not by ionising radiation. The results of this study show that folate status has an important impact on chromosomal stability and is an important modifying factor of cellular sensitivity to radiation-induced genome damage

  13. Comparison of prenatal diagnostic indications of trisomy 18%18-三体的产前诊断指征比较

    Institute of Scientific and Technical Information of China (English)

    曾艳; 许平; 范佳鸣; 张丽芳

    2012-01-01

    Objective: To evaluate the prenatal diagnostic indications of trisomy 18. Methods; The cases who received prenatal diagnosis in the hospital from 2004 to 2008 were analyzed retrospectively, then they were divided into different groups according to prenatal diagnostic indications; advanced age group (786 patients) , trisomy 18 high risk group (115 patients) , and abnormal ultrasonography group (90 patients) ; 15 cases with trisomy 18 screened out during the period and 2 cases with trisomy 18 found after birth were analyzed. Results; The detection rate of trisomy 18 in abnormal ultrasonography group was the highest (5. 56% ) , the detection rate of trisomy 18 in advanced age group was the lowest (0. 51% ) . Among 17 cases with trisomy 18, 14 cases were found with trisomy 18 of complete type, and 3 cases were found with trisomy 18 of translocation type. Conclusion; The most sensitive indication for prenatal diagnosis of trisomy 18 is still ultrasonography.%目的:对18-三体的产前诊断指征进行评估.方法:对2004 ~ 2008年间产前诊断病人进行回顾性分析,根据产前诊断指征进行分组,其中高龄组786例,18-三体高风险组115例,超声检测异常组90例,并对这期间产前诊断出的15例及出生的2例18-三体进行分析.结果:超声异常组18-三体检出率最高(5.56%),高龄组的检出率最低(0.51%).17例18-三体中完全型18-三体14例,3例易位型.结论:18-三体产前诊断最敏感的指征仍是超声检查.

  14. Non-invasive prenatal diagnosis of fetal trisomy 21 using cell-free fetal DNA in maternal blood

    OpenAIRE

    Lim, Ji Hyae; Park, So Yeon; Ryu, Hyun Mee

    2013-01-01

    Since the existence of cell-free fetal DNA (cff-DNA) in maternal circulation was discovered, it has been identified as a promising source of fetal genetic material in the development of reliable methods for non-invasive prenatal diagnosis (NIPD) of fetal trisomy 21 (T21). Currently, a prenatal diagnosis of fetal T21 is achieved through invasive techniques, such as chorionic villus sampling or amniocentesis. However, such invasive diagnostic tests are expensive, require expert technicians, and...

  15. Constitutional Mosaic Trisomy 13 in Two Germ Cell Layers is Different from Patau Syndrome? A Case Report

    OpenAIRE

    Kunwar, Fulesh; Pandya, Vidhi; Bakshi, Sonal R.

    2016-01-01

    The heterogeneous phenotype of known syndromes is a clinical challenge, and harmonized description using globally accepted ontology is desirable. This report attempts phenotypic analysis in a patient of constitutional mosaic trisomy 13 in mesoderm and ectoderm to make globally comparable clinical description. Phenotypic features (minor/major abnormalities) were recorded and matched with the Human Phenotype Ontology terms that were used to query web-based tool Phenomizer. We report here a case...

  16. Case Report: CD19-positive acute myeloblastic leukemia with trisomy 21 as a sole acquired karyotypic abnormality

    Institute of Scientific and Technical Information of China (English)

    Hua-feng WANG; Yi-zhi CHENG; Huan-ping WANG; Zhi-mei CHEN; Ji-yu LOU; Jie JIN

    2009-01-01

    We report that a 63-year-old Chinese female had acute myeloblastic leukemia (AML) in which trisomy 21 (+21) was found as the sole acquired karyotypic abnormality. The blasts were positive for myeloperoxidase, and the immunophenotype was positive for cluster of differentiation 19 (CDI9), CD33, CD34, and human leukocyte antigens (HLA)-DR. The chromosomal analysis of bone marrow showed 47,XX,+21 [2]/46,XX[18]. Fluorescent in situ hybridization (FISH) showed that three copies of AML1 were situated in separate chromosomes, and that t(8;21) was negative. The patient did not have any features of Down syndrome. A diagnosis of CD19-positive AML-M5 was established with trisomy 21 as a sole acquired karyotypic abnormality. The patient did not respond well to chemotherapy and died three months after the diagnosis. This is the first reported case of CD19-positive AM L with trisomy 21 as the sole cytogenetic abnormality. The possible prognostic significance of the finding in AML with +21 as the sole acquired karyotypic abnormality was discussed.

  17. CLINICAL PERFORMANCE CHARACTERISTICS OF ELECSYS® FREE-ΒHCG AND PAPP-A FOR FIRST TRIMESTER TRISOMY 21 RISK ASSESSMENT IN GESTATIONAL WEEKS 8+0 TO 14+0

    DEFF Research Database (Denmark)

    Tørring, Niels; aulesa, C; Eiben, Bernd;

    2014-01-01

    Background Screening for fetal trisomy 21 (T21) in the first trimester includes analysis of the serological markers pregnancy-associated plasma protein A (PAPP-A) and free beta choriogonadotropin (free βhCG). With the launch of these assays on the cobas e and Elecsys platforms, we investigated...... their clinical and analytical performance. Patients and Methods We conducted a multicenter study in 5397 pregnancies including 108 cases with verified fetal T21 at 8 to 14 weeks of gestation. A technical validation of the Roche Elecsys® free βhCG and PAPP-A assays were performed, including method comparisons...... with the Brahms Kryptor®, PerkinElmer AutoDELFIA® and Siemens IMMULITE® assays. Furthermore a clinical validation including generation of assay specific medians from gestational age 8+0 to 14+0 weeks, and clinical test performance of risk assessment was performed. Results The imprecision of the Elecsys free βh...

  18. 荧光原位杂交技术检测自然流产组织染色体非整倍体%Detection of chromosomal aneuploidies in spontaneous abortion samples by fluorescence in situ hybridization

    Institute of Scientific and Technical Information of China (English)

    魏萍; 李运星; 陈春; 曾兰; 秦胜芳; 汪雪雁; 席娜

    2015-01-01

    目的 探讨荧光原位杂交(fluorescence in situ hybridization,FISH)技术在自然流产组织染色体非整倍体检测中的价值和自然流产患者中染色体非整倍体比例.方法 对81份自然流产组织标本进行13、21和16、22及18、X、Y三组染色体探针的FISH检测.结果 81份自然流产组织中成功标记80份,检测成功率98.77%,其中异常标本35例,异常检出率43.75%,分别为常染色体三体19例,性染色体单体6例,三倍体9例,四倍体1例.结论 FISH技术用于自然流产组织染色体非整倍体分析具有快速、简便等优点,FISH分析可满足染色体非整倍体分析的需要;早期的自然流产病例中染色体非整倍体占较大的比例.%Objective To analyze 81 spontaneous abortion samples with fluorescence in situ hybridization (FISH).Methods Chromosome 13,21,16,22,18,X and Y probes were used to detect the samples.Results FISH was successful in 80 cases (98.77%).Among these,35 (43.75%) had an abnormal karyotype,which included 19 autosomal aneuploidies,6 sex chromosome aneuploidies,9 triploidies and 1 tetraploidy.Conclusion FISH is a rapid and easy method for detecting chromosomal aneuploidies in spontaneous abortion samples,and has a higher detection rate in early spontaneous abortion samples.

  19. Identification of novel candidate gene loci and increased sex chromosome aneuploidy among infants with conotruncal heart defects.

    Science.gov (United States)

    Osoegawa, Kazutoyo; Iovannisci, David M; Lin, Bin; Parodi, Christina; Schultz, Kathleen; Shaw, Gary M; Lammer, Edward J

    2014-02-01

    Congenital heart defects (CHDs) are common malformations, affecting four to eight per 1,000 total births. Conotruncal defects are an important pathogenetic subset of CHDs, comprising nearly 20% of the total. Although both environmental and genetic factors are known to contribute to the occurrence of conotruncal defects, the causes remain unknown for most. To identify novel candidate genes/loci, we used array comparative genomic hybridization to detect chromosomal microdeletions/duplications. From a population base of 974,579 total births born during 1999-2004, we screened 389 California infants born with tetralogy of Fallot or d-transposition of the great arteries. We found that 1.7% (5/288) of males with a conotruncal defect had sex chromosome aneuploidy, a sevenfold increased frequency (relative risk = 7.0; 95% confidence interval 2.9-16.9). We identified eight chromosomal microdeletions/duplications for conotruncal defects. From these duplications and deletions, we found five high priority candidate genes (GATA4, CRKL, BMPR1A, SNAI2, and ZFHX4). This is the initial report that sex chromosome aneuploidy is associated with conotruncal defects among boys. These chromosomal microduplications/deletions provide evidence that GATA4, SNAI2, and CRKL are highly dosage sensitive genes involved in outflow tract development. Genome wide screening for copy number variation can be productive for identifying novel genes/loci contributing to non-syndromic common malformations.

  20. Aneuploidy analysis of non-pronuclear embryos from IVF with use of array CGH: a case report.

    Science.gov (United States)

    Lixin, Deng; Zhifeng, Xiang; Cong, He; Jinzhou, Zhang; Hongbin, Xie

    2014-06-01

    By using array comparative genomic hybridization (array CGH), to analyze the aneuploidy of the single blastomeres from non-pronuclear embryos on cleavage-stage in IVF cycle. Four non-pronuclear embryos were got from an IVF cycle, and the each single cell was biopsied from the four cleavage-stage embryos on the third day after the insemination which was investigated by using array CGH. After the biopsy, all the embryos continued to cleave, and lately entered the morula stage on the fifth day, just one embryo 3 was developed to early blastocyst stage on the sixth day. The four blastomere 24 chromosomes showed one X monomer and three normal XY diploids; the autosome chromosomes of blastomeres were abnormally gained or lost at different chromosome from four embryos, such as Embryo 1 : 49,X (-1, -5, -11, -19, -20, -21, -Y, +3, +6, +7, +8, +10, +13, +14, +16, +17, +18); Embryo 2 : 44,XY (-12, -15); Embryo 3: 47,XY (-3, -8, -9, -21, +7, +17, +18, +19, +20); Embryo 4 : 54,XY (+4, +7, +10, +12, +13, +16, +17, +22). With the use of the array CGH, the aneuploidy analysis could review the abnormal chromosomes of single blastomere from the non-pronuclear embryos, which can harbor the risk of abnormal sex chromosome and autosome chromosomes.

  1. Aneuploidy does not explain the difference in outcomes observed between Asian and Caucasian patients undergoingin vitro fertilization

    Institute of Scientific and Technical Information of China (English)

    Jonathan Kort; David Smotrich; Michelle Gaona; XiaWang; BarryBehr

    2015-01-01

    Objective:To understand whether reduced pregnancy and live birth rates for Asian patients undergoing in vitro fertilization (IVF) could be explained by discrepant rates of aneuploid embryos.Methods:A retrospective cohort study of all autologous and donor IVF cycles utilizing pre-implantation genetic screening (PGS) at a single infertility clinic from January 2012 to December 2013.Results:After controlling for maternal age, there was no difference in aneuploidy rates of Caucasian patients compared to Asian patients’. A trend was discerned that embryos of Caucasians form blastocysts more frequently than those of Asian patients, reaching significance for patients aged 25 to 30 and 40 to 45, but there was no difference in the likelihood of having at least one euploid blastocyst to transfer in any age group. Conclusion:While there may be a slight difference in blastocyst formation rates, there is no difference in aneuploidy or euploid blastocyst transfer rates between Asian and Caucasian patients that would explain the discrepancy in IVF outcomes observed between these patient populations. Possible ethnicity specific differences in non-ploidy related embryo viability and endometrial receptivity should be investigated as potential etiologies for this observation.

  2. Maternal SNPs in the p53 Pathway: Risk Factors for Trisomy 21?

    Directory of Open Access Journals (Sweden)

    Juliano André Boquett

    2013-01-01

    Full Text Available The p53 family and its regulatory pathway play an important role as regulators of developmental processes, limiting the propagation of aneuploid cells. Its dysfunction or imbalance can lead to pathological abnormalities in humans. The aim of this study was to evaluate the effect of maternal polymorphisms TP53 c.215G>C (P72R, TP73 4 c.-30G>A and 14 c.-20C>T, MDM2 c.14+309T>G (SNP309, MDM4 c.753+572C>T and USP7 c.2719-234G>A as risk factors for Down Syndrome (DS birth. A case-control study was conducted with 263 mothers of DS children and 196 control mothers. The distribution of these genotypic variants was similar between case and control mothers. However, the combined alleles TP53 C and MDM2 G, and TP53 C and USP7 A increased the risk of having offspring with DS (OR = 1.84 and 1.77; 95% CI; P < 0.007 and 0.018, respectively. These results suggest that, although the individual polymorphisms were not associated with DS birth, the effect of the combined genotypes among TP53, MDM2 and USP7 genes indicates a possible role of TP53 and its regulatory pathway as a risk factor for aneuploidy.

  3. Liveborn with both partial trisomy of 3q and partial monosomy of 9p

    Energy Technology Data Exchange (ETDEWEB)

    Farren-Chavez, D.M.; Guzman, E.R. [UMDNJ-Robert Wood Johnson Medical School and St. Peter`s Medical Center, New Brunswich, NJ (United States); Peters, T.L. [Duke Univ., Durham, NC (United States)] [and others

    1994-09-01

    A 32-year-old G{sub 3}P{sub 2002} Hispanic female presented at 14 weeks gestation for routine dating ultrasound. At that time ultrasonography revealed a septated cystic hygroma, omphalocele, bilateral talipes equinovarus, and hydrops. Amniocentesis was performed at 15 weeks and revealed a 46,XX,9p+ chromosome complement. The origin of the extra material on the terminal short arm of chromosome 9 could not be identified. Chromosome analysis was performed on the parents and the mother was found to carry the balanced translocation 46,XX,p(3;9)(q23;p13). Further analysis revealed that the fetus had inherited the derivative 9 chromosome. The fetus was therefore monosomic for 9p13-9pter and trisomic for 3q23-3pter. The patient chose to continue the pregnancy. Serial ultrasonography later demonstrated a sloping forehead, small nose, micrognathia, ventriculomegaly, possible VSD, micropenis, hypospadias, cryptorchidism and post-axial polydactyly of the hands. The fetus was delivered prematurely at 31 weeks and survived one hour. Post-mortem examination confirmed the ultrasound findings and revealed additional stigmata consistent with both 9p monosomy and 3q trisomy. A review of the literature indicates no previous report of both syndromes concurrently.

  4. Pigmentary mosaicism following the lines of Blaschko in a girl with a double aneuploidy mosaicism : (47,XX,+7/45,X)

    NARCIS (Netherlands)

    Niessen, RC; Jonkman, MF; Muis, N; Hordijk, R; van Essen, AJ

    2005-01-01

    We report on a 6-year-old girl with linear streaks of apparent hypopigmentation and hyperpigmentation following the Blaschko lines, growth retardation, bupthalmos of the left eye, and mild mental retardation. She had a 45,X karyotype in lymphocytes. In cultured fibroblasts a double aneuploidy mosaic

  5. Elevated level of spindle checkprotein MAD2 correlates with cellular mitotic arrest, but not with aneuploidy and clinicopathological characteristics in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Chew-Wun Wu; Chin-Wen Chi; Tze-Sing Huang

    2004-01-01

    AIM: To study the relevance of spindle assembly checkprotein MAD2 to cellular mitotic status, aneuploidy and other clinicopathological characteristics in gastric cancer.METHODS: Western blot analyses were performed to analyze the protein levels of MAD2 and cyclin B1 in the tumorous and adjacent nontumorous tissues of 34 gastric cancer patients. Cell cycle distribution and DNA ploidy of cancer tissues were also determined by flow cytometry.Conventional statistical methods were adopted to determine the relevance of abnormal MAD2 level to mitotic status,aneuploidy and clinicopathological parameters.RESULTS: Out of 34 gastric cancer patients 25 (74%)exhibited elevated MAD2 levels in their tumorous tissues compared with the corresponding nontumorous tissues.Elevation of MAD2 levels significantly correlated with the increased levels of cydin B1 expression and G2/M-phase distribution (P = 0.038 and P = 0.033, respectively), but was not relevant to aneuploidy. The gastric cancer patients with elevated MAD2 levels showed a tendency toward better disease-free and overall survival (P>0.05). However, no association was found between elevated MAD2 levels and patients' clinicopathological characteristics.CONCLUSION: Elevation of MAD2 level is present in 74%of gastric cancer patients, and correlates with increased mitotic checkpoint activity. However, elevation of MAD2level is not associated with patients' aneuploidy and any of the clinicopathological characteristics.

  6. Detection of DNA Aneuploidy in Exfoliated Airway Epithelia Cells of Sputum Specimens by the Automated Image Cytometry and Its Clinical Value in the Identification of Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    杨健; 周宜开

    2004-01-01

    To evaluate the value of detecton of DNA aneuploidy in exfoliated airway epithelia cells of sputum specimens by the automated image cytometry for the identification of lung cancer, 100patients were divided into patient group (50 patients with lung cancer)and control group (30 patients with tuberculosis and 20 healthy people). Sputum was obtained for the quantitative analysis of DNA content of exfoliated airway epithelial cells with the automated image cytometry, together with the examinations of brush cytology and conventional sputum cytology. Our results showed that DNA aneuploidy (DI>2.5 or 5c) was found in 20 out of 50 sputum samples of lung cancer, 1 out of 30 sputum samples from tuberculosis patients, and none of 20 sputum samples from healthy people. The positive rates of conventional sputum cytology and brush cytology were 16 % and 32 %,which was lower than that of DNA aneuploidy detection by the automated image cytometry (P<0.01 ,P>0.05). Our study showed that automated image cytometry, which uses DNA aneuploidy as a marker for tumor, can detect the malignant cells in sputum samples of lung cancer and it is a sensitive and specific method serving as a complement for the diagnosis of lung cancer.

  7. Immunoreactive Cu-SOD and Mn-SOD in lymphocytes sub-populations from normal and trisomy 21 subjects according to age

    International Nuclear Information System (INIS)

    Copper and manganese superoxide dismutases (Cu-SOD and Mn-SOD) were measured by radioimmunoassay in B and T lymphocytes and macrophages, in patients with trisomy 21 and in matched controls. In the controls, Cu-SOD was present in greater amounts than Mn-SOD and there were quantitative differences in the distribution in the three cellular sub-populations. In trisomy 21, levels of Cu-SOD were raised, with no change in levels of Mn-SOD, supporting the theory of a gene dosage effect. There were significant positive and negative correlations between age and Cu-SOD levels in controls, and a correlation approaching significance for Mn-SOD. In trisomy 21, there was no correlation between age and Cu-SOD levels, and the only significant correlation for Mn-SOD was for B lymphocytes

  8. Trisomy 12 is seen within a specific subtype of B-cell chronic lymphoproliferative disease affecting the peripheral blood/bone marrow and co-segregates with elevated expression of CD11a.

    Science.gov (United States)

    Su'ut, L; O'Connor, S J; Richards, S J; Jones, R A; Roberts, B E; Davies, F E; Fegan, C D; Jack, A S; Morgan, G J

    1998-04-01

    In order to delineate the specific morphological and immunophenotypic features of B-cell lymphoproliferative disorders associated with trisomy 12, 172 sequential unselected cases of CD19+CD5+ B-cell disorders, primarily affecting the peripheral blood and bone marrow, were studied. Trisomy 12 was found in 24 cases (13.9%), with all cases morphologically classified as either CLL-PL or CLL-mixed by FAB criteria. Trisomy 12 was not found in any cases of typical CLL. Trisomy 12 cases demonstrated a significant higher expression of CD11a (P<0.0001) and CD20 (P<0.0006) when compared to cases with the equivalent morphology and immunophenotype, but without the chromosomal abnormality. Trisomy 12 cases also demonstrated a higher frequency of FMC7, CD38 expression and moderate to strong surface immunoglobulin staining. However, no correlation was detected between the percentages of trisomy 12 cells and cells expressing CD11a, CD38, FMC7 or sIg mean fluorescent intensity. Cells from trisomy 12 positive cases were sorted according to their CD11a expression using fluorescent activated cell sorting. There was a significant increase in the percentage of trisomy 12 cells within the CD11a+ sorted fraction compared to the unsorted population (P < 0.05), implying that trisomy 12 is associated with increased expression of CD11a. With the highly specific morphological and immunophenotypic features demonstrated by trisomy 12 cases in this study, it is highly likely that these cases constitute a specific group of B-cell lymphoproliferative disorders.

  9. Pre-weaning sensorial and motor development in mice transpolygenic for the critical region of trisomy 21.

    Science.gov (United States)

    Roubertoux, Pierre L; Bichler, Zoë; Pinoteau, Walter; Jamon, Marc; Sérégaza, Zohra; Smith, Desmond J; Rubin, Edward; Migliore-Samour, Danièle

    2006-05-01

    Trisomy 21 occurs every 1/800 births and is the most frequent genetic cause of mental retardation. Children with trisomy 21 show delayed sensorial and motor development as well as cognitive disorders. We selected a mouse model of trisomy 21 (TRS21): transgenic mice carrying extra copies of a HSA21 region corresponding to the D21S17-ETS2 region (previously referred to as "Down syndrome critical region 1"). Sensorial and motor development was measured in these partially transgenic mice, from birth to weaning. The four HSA21 regions contributed unequally to sensorial and motor development delay. The more centromeric region (230E8) modified 4 of the development indicators plus the size of the effect, indicated by partial eta(2)(eta(p)(2), reached a median value of 14.5%. The neighboring 141G6 region contributed to 5 developmental differences (eta(p)(2) median value 14%). The most telomeric region (285E6) only modified one development indicator. An extra copy of an HSA21 fragment (referred to here as the 152F7 region) induced modifications to 14 of the 18 indicators measured with a eta(2) median value reaching 20%. The results indicate a noticeable contribution of the 152F7 region to sensorial and motor development. The contribution of this region to cognitive functioning and its neurobiological basis has been already reported. This set of result suggests the location in the D21S17-ETS2 region of several genes playing crucial role in cognitive and developmental impairment observed in TRS21. PMID:16514474

  10. Dynamic Bcl-xL (S49) and (S62) Phosphorylation/Dephosphorylation during Mitosis Prevents Chromosome Instability and Aneuploidy in Normal Human Diploid Fibroblasts

    Science.gov (United States)

    Baruah, Prasamit Saurav; Beauchemin, Myriam; Hébert, Josée; Bertrand, Richard

    2016-01-01

    Bcl-xL proteins undergo dynamic phosphorylation/dephosphorylation on Ser49 and Ser62 residues during mitosis. The expression of Bcl-xL(S49A), (S62A) and dual (S49/62A) phosphorylation mutants in tumor cells lead to severe mitotic defects associated with multipolar spindle, chromosome lagging and bridging, and micro-, bi- and multi-nucleated cells. Because the above observations were made in tumor cells which already display genomic instability, we now address the question: will similar effects occur in normal human diploid cells? We studied normal human diploid BJ foreskin fibroblast cells expressing Bcl-xL (wild type), (S49A), (S49D), (S62A), (S62D) and the dual-site (S49/62A) and (S49/62D) mutants. Cells expressing S49 and/or S62 phosphorylation mutants showed reduced kinetics of cell population doubling. These effects on cell population doubling kinetics correlated with early outbreak of senescence with no impact on the cell death rate. Senescent cells displayed typical senescence-associated phenotypes including high-level of senescence-associated β-galactosidase activity, interleukin-6 (IL-6) secretion, tumor suppressor p53 and cyclin-dependent kinase inhibitor p21Waf1/Cip1 activation as well as γH2A.X-associated nuclear chromatin foci. Fluorescence in situ hybridization analysis and Giemsa-banded karyotypes revealed that the expression of Bcl-xL phosphorylation mutants in normal diploid BJ cells provoked chromosome instability and aneuploidy. These findings suggest that dynamic Bcl-xL(S49) and (S62) phosphorylation/dephosphorylation cycles are important in the maintenance of chromosome integrity during mitosis in normal cells. They could impact future strategies aiming to develop and identify compounds that could target not only the anti-apoptotic domain of Bcl-xL protein, but also its mitotic domain for cancer therapy. PMID:27398719

  11. First-trimester risk calculation for trisomy 13, 18, and 21: comparison of the screening efficiency between 2 locally developed programs and commercial software

    DEFF Research Database (Denmark)

    Sørensen, Steen; Momsen, Günther; Sundberg, Karin;

    2011-01-01

    Reliable individual risk calculation for trisomy (T) 13, 18, and 21 in first-trimester screening depends on good estimates of the medians for fetal nuchal translucency thickness (NT), free β-subunit of human chorionic gonadotropin (hCGβ), and pregnancy-associated plasma protein-A (PAPP-A) in mate......Reliable individual risk calculation for trisomy (T) 13, 18, and 21 in first-trimester screening depends on good estimates of the medians for fetal nuchal translucency thickness (NT), free β-subunit of human chorionic gonadotropin (hCGβ), and pregnancy-associated plasma protein-A (PAPP...

  12. First-trimester risk calculation for trisomy 13, 18, and 21: comparison of the screening efficiency between 2 locally developed programs and commercial software

    DEFF Research Database (Denmark)

    Sørensen, Steen; Momsen, Günther; Sundberg, Karin;

    2011-01-01

    Reliable individual risk calculation for trisomy (T) 13, 18, and 21 in first-trimester screening depends on good estimates of the medians for fetal nuchal translucency thickness (NT), free ß-subunit of human chorionic gonadotropin (hCGß), and pregnancy-associated plasma protein-A (PAPP-A) in mate......Reliable individual risk calculation for trisomy (T) 13, 18, and 21 in first-trimester screening depends on good estimates of the medians for fetal nuchal translucency thickness (NT), free ß-subunit of human chorionic gonadotropin (hCGß), and pregnancy-associated plasma protein-A (PAPP...

  13. Maternal uniparental disomy of chromosome 2 in a baby with trisomy 2 mosaicism in amniotic fluid culture

    Energy Technology Data Exchange (ETDEWEB)

    Harrison, K. [Morristown Memorial Hospital, NJ (United States); Eisenger, K.; Brown, S. [Columbia Univ., New York, NY (United States)] [and others

    1995-08-28

    We describe the first case of a baby with maternal uniparental disomy of chromosome 2. Growth failure, hypothyroidism, and hyaline membrane disease were present at birth, and the first year of life was complicated by bronchopulmonary dysplasia. At age 14 months, motor and intellectual development were normal, but growth remained below the 10th centile. The baby was investigated for uniparental disomy because trisomy 2 mosaicism had been detected in a second trimester amniocentesis. This is the first reported case in which amniotic fluid chromosome mosaicism has been associated with uniparental disomy. Implications for prenatal diagnosis are considered. 26 refs., 4 figs.

  14. Maternal uniparental disomy of chromosome 2 in a baby with trisomy 2 mosaicism in amniotic fluid culture

    Energy Technology Data Exchange (ETDEWEB)

    Harrison, K.B. [Morristown Memorial Hospital, NJ (United States); Eisenger, K.; Brown, S. [Columbia Univ., NY (United States)] [and others

    1994-09-01

    We describe the first case of a baby with maternal uniparental disomy for chromosome 2. Growth failure, hypothyroidism and hyaline membrane disease were present at birth, and the first year of life was complicated by bronchopulmonary dysplasia. At 14 months, motor and intellectual development appear to be normal, but growth remains below the 10th percentile. The baby was investigated for uniparental disomy because trisomy 2 mosaicism had been detected in a second trimester amniocentesis. This is the first reported case in which amniotic fluid chromosome mosaicism has been associated with uniparental disomy. Implications for prenatal diagnosis are considered.

  15. Familial translocation t(6;20)(p21;p13) resulting in partial trisomy 6p and partial monosomy 20p: report of a new case and review of the literature.

    Science.gov (United States)

    Berner, A L; Bağci, S; Wohlleber, E; Engels, E; Müller, A; Bartmann, P; Weber, R G; Reutter, H

    2012-01-01

    Carriers of completely balanced chromosomal translocations have all necessary genetic information. Nevertheless, because of the possibility of maldistribution during gametogenesis, they are at increased risk for infertility, miscarriage, stillbirth or having a child with congenital anomalies including mental retardation. As postnatal clinical reports are infrequent, prediction of clinical course for specific unbalanced karyotypes diagnosed during pregnancy remains difficult. Here, we report the 6th case of partial trisomy 6p and partial monosomy 20p due to an unbalanced adjacent-1 segregation of the rare familial translocation t(6;20)(p21;p13). We give a thorough clinical description of the present case, demonstrating broad phenotypic overlap with the 5 previously published cases reviewed here, providing important data on postnatal outcome.

  16. Expression signature as a biomarker for prenatal diagnosis of trisomy 21.

    Directory of Open Access Journals (Sweden)

    Marija Volk

    Full Text Available A universal biomarker panel with the potential to predict high-risk pregnancies or adverse pregnancy outcome does not exist. Transcriptome analysis is a powerful tool to capture differentially expressed genes (DEG, which can be used as biomarker-diagnostic-predictive tool for various conditions in prenatal setting. In search of biomarker set for predicting high-risk pregnancies, we performed global expression profiling to find DEG in Ts21. Subsequently, we performed targeted validation and diagnostic performance evaluation on a larger group of case and control samples. Initially, transcriptomic profiles of 10 cultivated amniocyte samples with Ts21 and 9 with normal euploid constitution were determined using expression microarrays. Datasets from Ts21 transcriptomic studies from GEO repository were incorporated. DEG were discovered using linear regression modelling and validated using RT-PCR quantification on an independent sample of 16 cases with Ts21 and 32 controls. The classification performance of Ts21 status based on expression profiling was performed using supervised machine learning algorithm and evaluated using a leave-one-out cross validation approach. Global gene expression profiling has revealed significant expression changes between normal and Ts21 samples, which in combination with data from previously performed Ts21 transcriptomic studies, were used to generate a multi-gene biomarker for Ts21, comprising of 9 gene expression profiles. In addition to biomarker's high performance in discriminating samples from global expression profiling, we were also able to show its discriminatory performance on a larger sample set 2, validated using RT-PCR experiment (AUC=0.97, while its performance on data from previously published studies reached discriminatory AUC values of 1.00. Our results show that transcriptomic changes might potentially be used to discriminate trisomy of chromosome 21 in the prenatal setting. As expressional alterations

  17. Malignant chondroblastoma presenting as a recurrent pelvic tumor with DNA aneuploidy and p53 mutation as supportive evidence of malignancy

    Energy Technology Data Exchange (ETDEWEB)

    Ostrowski, M.L. [Department of Pathology and Laboratory Medicine, Baylor College of Medicine, The Methodist Hospital and Texas Children' s Hospital, Houston, Texas (United States); Department of Pathology and Laboratory Medicine, Houston, TX (United States). Methodist Hospital; Johnson, M.E. [Department of Orthopedic Surgery, Baylor College of Medicine, The Methodist Hospital and Texas Children' s Hospital, Houston, Texas (United States); Truong, L.D.; Hicks, M.J.; Spjut, H.J. [Department of Pathology and Laboratory Medicine, Baylor College of Medicine, The Methodist Hospital and Texas Children' s Hospital, Houston, Texas (United States); Smith, F.E. [Department of Oncology, Baylor College of Medicine, The Methodist Hospital and Texas Children' s Hospital, Houston, Texas (United States)

    1999-11-01

    We report a rare case of malignant chondroblastoma, which presented in a 47-year-old man as a recurrent tumor, 18 years following wide excision of a typical pelvic chondroblastoma. Radiologic studies of the recurrent tumor showed a large, lytic, destructive lesion of the right pelvic bones and femur, with a pathologic fracture of the latter, a large pelvic soft tissue mass, and multiple pulmonary metastases. Biopsy tissue showed typical features of chondroblastoma, but also increased nuclear atypia, hyperchromasia, and pleomorphism, compared to the original tumor, and, most significantly, abnormal mitotic figures. Immunohistochemical studies of the recurrent tumor revealed p53 mutation and extensive proliferative activity, and flow cytometric studies showed DNA aneuploidy, none of which was present in the original tumor. The patient received chemotherapy and radiation, but died of disease eight months after presentation. We also review chondroblastoma in general, to assign this unusual lesion to a tumor subtype. (orig.)

  18. Rapid detection of chromosome 18 aneuploidies in amniocytes by using primed in situ labeling (PRINS) technique

    Institute of Scientific and Technical Information of China (English)

    杨建滨; 郑树

    2002-01-01

    This paper presents a feasible method for rapid detection of the interphase nuclei of uncultured amniocytes for chromosomes 18 by using our modified in situ labeling (PRINS) technique.A total of 262 independent,uncultured amniotic fluid samples were analysed in a blind fashion before the karyotype was available.In addition,62 samples were examined by fluorescence in situ hybridization (FISH) for comparison.In more than 95% of the samples PRINS reactions with primer 18cen were successfully induced.Two samples were properly identified and correctly scored as trisomic 18.PRINS reaction could be performed automatically in less than one hour with a propgrammable thernocycler.Our studies showed that the PRINS technique is simple.rapid and cost-effective.It is as sensitive and specific as FISH;can enhance the eccuracy of standard cytogenetic analysis;and allows identification of chromosomes 18 aneuploidies in uncultrued amniocytes in significantly less time.

  19. 18,X,Y aneuploidies and transmission electron microscopy studies in spermatozoa from five carriers of different reciprocal translocations

    Institute of Scientific and Technical Information of China (English)

    Elena Moretti; Nicola Antonio Pascarelli; Valentina Giannerini; Michela Geminiani; Cecilia Anichini; Oiulia Collodel

    2009-01-01

    We analysed ejaculated spermatozoa from five infertile men with different balanced reciprocal translocations to contribute to the study of meiotic segregation of chromosomes 18, X and Y and also to evaluate sperm morphology by transmission electron microscopy (TEM) analysis. Conventional lymphocyte karyotype analyses highlighted dif-ferent reciprocal balanced translocations: t(12; 13), t(4;9), t(X;8), t(8; 10) and t(3; 16). Semen analysis was performed by light and TEM. Fluorescence in situ hybridization was performed directly on sperm nuclei using centromeric probes for chromosomes 18, X and Y. The carriers of the balanced reciprocal translocations considered in the pres-ent study showed a very similar pattern of sperm pathologies: diffused presence of apoptosis and immaturity. All patients showed meiotic segregation derangements, highlighted by the presence of sperm diploidies and sex chro-mosome disomies particularly related to the failure of the first meiotic division. However, an increased incidence of chromosome 18 aneuploidy was detected in spermatozoa from t(X;8) and t(8;10) carriers. We have also reported values from sex chromosomes such as t(X;8), although the X chromosome was involved in translocation. Since pa-tients with reciprocal translocations and spermatogenetic impairment are candidates for intracytoplasmic sperm in-jection cycles, the study of sperm parameters, and particularly of the level of aneuploidy rates, would provide better information for couples at risk and would contribute to the data in the literature for a better understanding of the ef-fects of chromosomal rearrangement on the whole meiotic process and, in particular, on chromosomes not involved in translocation.

  20. 应用多重连接依赖式探针扩增技术快速高通量诊断胎儿染色体非整倍体异常%Rapid and high-throughput multiplex ligation-dependent probe amplification for diagnosis of chromosome aneuploidy

    Institute of Scientific and Technical Information of China (English)

    唐少华; 毛义建; 陈向南; 徐雪琴; 谢番妮; 吴昊; 李焕铮; 吕建新

    2011-01-01

    them 92% were finished within three working days and 5% required more days for repeating. The test failure rate was 3%. The results confirmed that for the 38 detectable aneuploid samples,the probe reliability weighted mean ratio values were more than 4SD compared to normal diploids and the 2 suspected trisomy samples were more than 2SD. In this study, authors analyzed hybridization efficiencies of 8 probes for chromosome 21, and the presence of a trisomy was considered if at least 4 of the 8 probes gave probe ratio of >1.3. Conclusion The data suggested that MLPA is a rapid, simple and reliable method for large scale testing for aneuploidy of chromosomes 13, 18, 21, X, or Y in AF. The MLPA technology is complementary to AF culture and valuable for prenatal diagnosis.

  1. 超声在21-三体综合征产前筛查中的应用分析%Aanalysis of prenatal ultrasonography in screening for fetal trisomy 21

    Institute of Scientific and Technical Information of China (English)

    韩璐; 荆春丽; 王彦; 冯丽云; 顾颜

    2016-01-01

    目的 探讨超声在21-三体综合征产前筛查中的应用价值.方法 2009年1月至2014年6月在大连市妇幼保健院被确诊为21-三体综合征的胎儿共77例,其中55例行超声筛查,分析其超声表现与21-三体综合征的关系.结果 55例接受产前超声筛查的21-三体综合征病例中,10例进行了孕早期超声筛查,8例(80%)发现异常;45例进行了孕中晚期超声筛查,37例(82.2%)发现超声异常.孕早期常见的异常为NT增厚(80%)、鼻骨缺失(40%)和静脉导管α波倒置(30%).孕中晚期常见的软指标异常为鼻骨缺失或发育不良(40.0%)、颈后皮肤皱褶增厚(26.7%)、肱骨或股骨短(17.8%)等;胎儿结构畸形主要为心血管畸形(33.3%)和十二指肠闭锁(13.3%)等.此外,21-三体综合征胎儿中晚期超声还可表现为羊水多(17.8%)和脐动脉血流异常(8.9%).结论 超声在21-三体综合征产前筛查中具有重要作用.%Objective:To investigate the clinical value of ultrasound in screening for fetal trisomy 21.Methods:From Jan.2009 to Jun.2014,77 fetuses was diagnosed as trisomy 21 in the Dalian Matemal and Child Health Hospital.In all cases,55 cases underwent prenatal ultrasound screening.The relationship between trisomy 21 and ultrasonic manifestations was analyzed.Results:In the 55 cases,10 cases were screened in early pregnancy.Sonographic anomalies were detected in 8 feruses (80%),including thickened nuehal translucency (80%),nasal bone hypoplasia (40%),reverse of a-wave of ductus venosus (30%) and so on.45 cases were screened in middle and late pregnancy.Sonographic anomalies were detected in 37 feruses (82.2%).The most common ultrasound markers were nasal bone hypoplasia (40%),thickened nuchal fold (26.7%) and short femurs and humerus (17.8%),the common structural malformations include cardiac defects (33.3%) and digestive system (13.3%).Furthermore,much amniotic fluid (17.8%) and abnormal umbilical artery

  2. 18-三体综合征胎儿母体血清学筛查及超声检查分析%Analysis of maternal serum screening and sonographic screening of fetuses with trisomy 18

    Institute of Scientific and Technical Information of China (English)

    吴晓霞; 袁晖; 张育森; 孙颖; 陈芳; 王晨虹

    2013-01-01

    目的 探讨胎儿18-三体综合征的母体血清学筛查和产前超声检查特征.方法 对我院2010年1月~2012年12月行产前诊断的16例18-三体综合征胎儿母体血清学筛查指标和产前超声表现特征进行总结分析.结果 18-三体综合征胎儿母体血清妊娠相关蛋白A (PAPPA)、绒毛膜促性腺激素(HCG)、甲胎蛋白(AFP)和非结合雌三醇(uE3)均低于正常值.16例18-三体综合征胎儿在产前超声检查中发现均有1项以上的结构畸形,其中最常见的3种超声异常为心脏畸形12例(75.00%),脉络丛囊肿9例(56.25%)和草莓头5例(31.25%);其他常见的畸形包括钩状手和重叠指各4例(25.00%),鼻骨未显示、小下颌、外耳畸形、单脐动脉各3例(18.75%),桡骨发育不良或缺如3例(18.75%),足内翻、摇椅足各2例(12.50%)等.结论 母体血清学筛查和产前超声联合筛查对于18-三体综合征胎儿的检出具有重要临床意义.%Objective:To evaluate the characteristics of maternal serum screening and prenatal ultrasound of fetus with trisomy 18.Methods:The maternal serum screening findings and prenatal sonographic features of 16 cases with trisomy 18 were retrospectively reviewed from January 2010 to December 2012.Results:Maternal serum screening markers demonstrated that trisomy 18 was identified by low levels of PAPP-A,HCG,AFP anduE3.All cases had at least one abnormal sonographic findings.The most three common abnormalities included cardiac anomalies (75.00%),choroid plexus cysts (56.25%) and strawberry head (31.25%) ; the other common abnormalities included utility hook (25.00%),finger overlap (25.00%),nasal bone absence (18.75%),micrognathia (18.75%),ear abnormalities (18.75%),single umbilical artery (18.75%),dysplasia or absence of radius (18.75%),talipes varus (12.50%) and rocker-bottom foot (12.50%) etc.Conclusions:Serological screening of pregnant women combined with fetal ultrasonography is an

  3. Trisomy 16q in a female newborn with a de novo X;16 translocation and hypoplastic left heart.

    Science.gov (United States)

    Bacino, C A; Lee, B; Spikes, A S; Shaffer, L G

    1999-01-15

    We report a case of a newborn female with minor dysmorphic features and hypoplastic left heart. Chromosome studies showed that she was the carrier of an unbalanced translocation between the X-chromosome and chromosome 16, resulting in monosomy for Xp and trisomy for 16q. Only a handful of partial trisomy 16q cases have been reported in the literature among liveborns. The great majority of these cases have had significant anomalies in contrast to what has been seen in our patient. The absence of dysmorphic features and other significant abnormalities in this case (with the exception to the hypoplastic left heart), suggested that the inactivation of the derivative X chromosome might have played a role in the mild phenotype of this patient. Conventional cytogenetic studies were conducted in this patient in conjunction with fluorescent in situ hybridization studies, which were used to characterize the X inactivation pattern. The studies revealed that the X chromosome material in the derivative chromosome was inactive while the chromosome 16 derived material in the derivative chromosome was early replicating and active in all cells studied.

  4. Interstitial deletion 5p accompanied by dicentric ring formation of the deleted segment resulting in trisomy 5p13-cen

    Energy Technology Data Exchange (ETDEWEB)

    Schuffenhauer, S.; Daumer-Haas, C.; Murken, J. [Ludwig-Maximilians-Universitaet Muenchen (Germany)] [and others

    1996-10-02

    Karyotypes with an interstitial deletion and a marker chromosome formed from the deleted segment are rare. We identified such a rearrangement in a newborn infant, who presented with macrocephaly, asymmetric square skull, minor facial anomalies, omphalocele, inguinal hernias, hypospadias, and club feet. The karyotype 46,XY,del(5)(pter{r_arrow}p13::cen{r_arrow}qter)/47,XY,+dicr(5)(:p13{r_arrow}cen::p13{r_arrow}cen),del(5)(pter{r_arrow}p13::cen{r_arrow}qter) was identified by banding studies and FISH analysis in the peripheral lymphocytes. One breakpoint on the del(5) maps distal to GDNF, and FISH analysis using an {alpha}-satellite probe suggests that the proximal breakpoint maps within the centromere. The dicentric r(5) consists of two copies of the segment deleted in the del(5), resulting in trisomy of proximal 5p (5p13-cen). The phenotype of the propositus is compared with other trisomy 5p cases and possible mechanisms for the generation of this unique chromosomal rearrangement are discussed. 27 refs., 3 figs.

  5. Altered expression of mitochondrial and extracellular matrix genes in the heart of human fetuses with chromosome 21 trisomy

    Directory of Open Access Journals (Sweden)

    Olla Carlo

    2007-08-01

    Full Text Available Abstract Background The Down syndrome phenotype has been attributed to overexpression of chromosome 21 (Hsa21 genes. However, the expression profile of Hsa21 genes in trisomic human subjects as well as their effects on genes located on different chromosomes are largely unknown. Using oligonucleotide microarrays we compared the gene expression profiles of hearts of human fetuses with and without Hsa21 trisomy. Results Approximately half of the 15,000 genes examined (87 of the 168 genes on Hsa21 were expressed in the heart at 18–22 weeks of gestation. Hsa21 gene expression was globally upregulated 1.5 fold in trisomic samples. However, not all genes were equally dysregulated and 25 genes were not upregulated at all. Genes located on other chromosomes were also significantly dysregulated. Functional class scoring and gene set enrichment analyses of 473 genes, differentially expressed between trisomic and non-trisomic hearts, revealed downregulation of genes encoding mitochondrial enzymes and upregulation of genes encoding extracellular matrix proteins. There were no significant differences between trisomic fetuses with and without heart defects. Conclusion We conclude that dosage-dependent upregulation of Hsa21 genes causes dysregulation of the genes responsible for mitochondrial function and for the extracellular matrix organization in the fetal heart of trisomic subjects. These alterations might be harbingers of the heart defects associated with Hsa21 trisomy, which could be based on elusive mechanisms involving genetic variability, environmental factors and/or stochastic events.

  6. Everyday executive functions in Down syndrome from early childhood to young adulthood: Evidence for both unique and shared characteristics compared to youth with sex chromosome trisomy (XXX and XXY

    Directory of Open Access Journals (Sweden)

    Nancy Raitano Lee

    2015-10-01

    Full Text Available Executive functions (EF are thought to be impaired in Down syndrome (DS and sex chromosome trisomy (Klinefelter and Trisomy X syndromes; +1X. However, the syndromic specificity and developmental trajectories associated with EF difficulties in these groups are poorly understood. The current investigation (a compared everyday EF difficulties in youth with DS, +1X, and typical development (TD; and (b examined relations between age and EF difficulties in these two groups and a TD control group cross-sectionally. Study 1 investigated the syndromic specificity of EF profiles on the Behavior Rating Inventory of Executive Function (BRIEF in DS (n=30, +1X (n=30, and a TD group (n=30, ages 5-18 years. Study 2 examined age effects on EF in the same cross-sectional sample of participants included in Study 1. Study 3 sought to replicate Study 2’s findings for DS by examining age-EF relations in a large independent sample of youth with DS (n=85 and TD (n=43, ages 4-24 years. Study 1 found evidence for both unique and shared EF impairments for the DS and +1X groups. Most notably, youth with +1X had relatively uniform EF impairments on the BRIEF scales, while the DS group showed an uneven BRIEF profile with relative strengths and weaknesses. Studies 2 and 3 provided support for fairly similar age-EF relations in the DS and TD groups. In contrast, for the +1X group, findings were mixed; 6 BRIEF scales showed similar age-EF relations to the TD group and 2 showed greater EF difficulties at older ages for +1X. These findings will be discussed within the context of efforts to identify syndrome specific cognitive-behavioral profiles for youth with different genetic syndromes in order to inform basic science investigations into the etiology of EF difficulties in these groups and to develop treatment approaches that are tailored to the needs of these groups.

  7. Everyday executive functions in Down syndrome from early childhood to young adulthood: evidence for both unique and shared characteristics compared to youth with sex chromosome trisomy (XXX and XXY).

    Science.gov (United States)

    Lee, Nancy Raitano; Anand, Payal; Will, Elizabeth; Adeyemi, Elizabeth I; Clasen, Liv S; Blumenthal, Jonathan D; Giedd, Jay N; Daunhauer, Lisa A; Fidler, Deborah J; Edgin, Jamie O

    2015-01-01

    Executive functions (EF) are thought to be impaired in Down syndrome (DS) and sex chromosome trisomy (Klinefelter and Trisomy X syndromes; +1X). However, the syndromic specificity and developmental trajectories associated with EF difficulties in these groups are poorly understood. The current investigation (a) compared everyday EF difficulties in youth with DS, +1X, and typical development (TD); and (b) examined relations between age and EF difficulties in these two groups and a TD control group cross-sectionally. Study 1 investigated the syndromic specificity of EF profiles on the Behavior Rating Inventory of Executive Function (BRIEF) in DS (n = 30), +1X (n = 30), and a TD group (n = 30), ages 5-18 years. Study 2 examined age effects on EF in the same cross-sectional sample of participants included in Study 1. Study 3 sought to replicate Study 2's findings for DS by examining age-EF relations in a large independent sample of youth with DS (n = 85) and TD (n = 43), ages 4-24 years. Study 1 found evidence for both unique and shared EF impairments for the DS and +1X groups. Most notably, youth with +1X had relatively uniform EF impairments on the BRIEF scales, while the DS group showed an uneven BRIEF profile with relative strengths and weaknesses. Studies 2 and 3 provided support for fairly similar age-EF relations in the DS and TD groups. In contrast, for the +1X group, findings were mixed; 6 BRIEF scales showed similar age-EF relations to the TD group and 2 showed greater EF difficulties at older ages for +1X. These findings will be discussed within the context of efforts to identify syndrome specific cognitive-behavioral profiles for youth with different genetic syndromes in order to inform basic science investigations into the etiology of EF difficulties in these groups and to develop treatment approaches that are tailored to the needs of these groups. PMID:26539087

  8. Everyday executive functions in Down syndrome from early childhood to young adulthood: evidence for both unique and shared characteristics compared to youth with sex chromosome trisomy (XXX and XXY).

    Science.gov (United States)

    Lee, Nancy Raitano; Anand, Payal; Will, Elizabeth; Adeyemi, Elizabeth I; Clasen, Liv S; Blumenthal, Jonathan D; Giedd, Jay N; Daunhauer, Lisa A; Fidler, Deborah J; Edgin, Jamie O

    2015-01-01

    Executive functions (EF) are thought to be impaired in Down syndrome (DS) and sex chromosome trisomy (Klinefelter and Trisomy X syndromes; +1X). However, the syndromic specificity and developmental trajectories associated with EF difficulties in these groups are poorly understood. The current investigation (a) compared everyday EF difficulties in youth with DS, +1X, and typical development (TD); and (b) examined relations between age and EF difficulties in these two groups and a TD control group cross-sectionally. Study 1 investigated the syndromic specificity of EF profiles on the Behavior Rating Inventory of Executive Function (BRIEF) in DS (n = 30), +1X (n = 30), and a TD group (n = 30), ages 5-18 years. Study 2 examined age effects on EF in the same cross-sectional sample of participants included in Study 1. Study 3 sought to replicate Study 2's findings for DS by examining age-EF relations in a large independent sample of youth with DS (n = 85) and TD (n = 43), ages 4-24 years. Study 1 found evidence for both unique and shared EF impairments for the DS and +1X groups. Most notably, youth with +1X had relatively uniform EF impairments on the BRIEF scales, while the DS group showed an uneven BRIEF profile with relative strengths and weaknesses. Studies 2 and 3 provided support for fairly similar age-EF relations in the DS and TD groups. In contrast, for the +1X group, findings were mixed; 6 BRIEF scales showed similar age-EF relations to the TD group and 2 showed greater EF difficulties at older ages for +1X. These findings will be discussed within the context of efforts to identify syndrome specific cognitive-behavioral profiles for youth with different genetic syndromes in order to inform basic science investigations into the etiology of EF difficulties in these groups and to develop treatment approaches that are tailored to the needs of these groups.

  9. Non-invasive epigenetic detection of fetal trisomy 21 in first trimester maternal plasma.

    Directory of Open Access Journals (Sweden)

    Ji Hyae Lim

    Full Text Available BACKGROUND: Down syndrome (DS is the most common known aneuploidy, caused by an extra copy of all or part of chromosome 21. Fetal-specific epigenetic markers have been investigated for non-invasive prenatal detection of fetal DS. The phosphodiesterases gene, PDE9A, located on chromosome 21q22.3, is completely methylated in blood (M-PDE9A and unmethylated in the placenta (U-PDE9A. Therefore, we estimated the accuracy of non-invasive fetal DS detection during the first trimester of pregnancy using this tissue-specific epigenetic characteristic of PDE9A. METHODOLOGY/PRINCIPAL FINDINGS: A nested, case-control study was conducted using maternal plasma samples collected from 108 pregnant women carrying 18 DS and 90 normal fetuses (each case was matched with 5 controls according to gestational weeks at blood sampling. All pregnancies were singletons at or before 12 weeks of gestation between October 2008 and May 2009. The maternal plasma levels of M-PDE9A and U-PDE9A were measured by quantitative methylation-specific polymerase chain reaction. M-PDE9A and U-PDE9A levels were obtained in all samples and did not differ between male and female fetuses. M-PDE9A levels did not differ between the DS cases and controls (1854.3 vs 2004.5 copies/mL; P = 0.928. U-PDE9A levels were significantly elevated in women with DS fetuses compared with controls (356.8 vs 194.7 copies/mL, P<0.001. The sensitivities of U-PDE9A level and the unmethylation index of PDE9A for non-invasive fetal DS detection were 77.8% and 83.3%, respectively, with a 5% false-positive rate. In the risk assessment for fetal DS, the adjusted odds ratios of U-PDE9A level and UI were 46.2 [95% confidence interval: 7.8-151.6] and 63.7 [95% confidence interval: 23.2-206.7], respectively. CONCLUSIONS: Our findings suggest that U-PDE9A level and the unmethylation index of PDE9A may be useful biomarkers for non-invasive fetal DS detection during the first trimester of pregnancy, regardless of fetal

  10. Cerebellar and brainstem hypoplasia in a child with a partial monosomy for the short arm of chromosome 5 and partial trisomy for the short arm of chromosome 10

    NARCIS (Netherlands)

    Arts, W F M; Hofstee, Y; Drejer, G F; Beverstock, G C; Oosterwijk, J C

    1995-01-01

    A child with hypoplasia of the cerebellum and brainstem in association with an unbalanced translocation, resulting in a partial deletion of the short arm of chromosome 5 and a partial trisomy of the short arm of chromosome 10, is described. A balanced translocation was present in his mother and mate

  11. Outcome after allogeneic transplantation for adult acute myeloid leukemia patients exhibiting isolated or associated trisomy 8 chromosomal abnormality : a survey on behalf of the ALWP of the EBMT

    NARCIS (Netherlands)

    Chevallier, P.; Labopin, M.; Nagler, A.; Ljungman, P.; Verdonck, L. F.; Volin, L.; Zander, A. R.; Finke, J.; Socie, G.; Cordonnier, C.; Harousseau, J-L; Mohty, M.; Rocha, V.

    2009-01-01

    The aim of this multicenter retrospective analysis was to carry out a survey of overall outcomes after allohematopoietic SCT of AML patients harboring trisomy 8 (+8) as the sole chromosomal abnormality or associated with other abnormalities. We have identified 182 de novo AML patients who underwent

  12. Clinical and molecular studies in full trisomy 22: Further delineation of the phenotype and review of the literature. Reply to Dr. Robinson and Dr. Kalousek

    Energy Technology Data Exchange (ETDEWEB)

    Bacino, C.A.; Graham, J.M. Jr. [UCLA School of Medicine, Los Angeles, CA (United States)

    1996-03-01

    This {open_quotes}Letter to the Editor{close_quotes} responds to the comments by Dr. Robinson and Dr. Kalousek regarding the implications of meiotic versus somatic chromosomal aberrations. The survival time of the patient may depend on the detection of mosicism; the discussion of the existence of full trisomy 22 remains controversial. 2 refs.

  13. Gastric low-grade MALT lymphoma, high-grade MALT lymphoma and diffuse large B cell lymphoma show different frequencies of trisomy

    NARCIS (Netherlands)

    Hoeve, M A; Gisbertz, I A; Schouten, H C; Schuuring, E; Bot, F J; Hermans, J; Hopman, A; Kluin, P M; Arends, J E; van Krieken, J H

    1999-01-01

    Gastric MALT lymphoma is a distinct entity related to Helicobacter pylori gastritis. Some studies suggest a role for trisomy 3 in the genesis of these lymphomas, but they mainly focused on low-grade MALT lymphoma. Gastric MALT lymphoma, however, comprises a spectrum from low- to high-grade cases. Fu

  14. Ti års erfaring med førstetrimester screening for føtal aneuploidi ved hjælp af biokemi fra gestationsuge 6+0 til 13+6

    DEFF Research Database (Denmark)

    Tørring, Niels; Petersen, Olav Bjørn; Uldbjerg, Niels

    2014-01-01

    i gestationsugerne 8-10. Formål At validere resultaterne af det danske screeningsprogram af første trimester screening for føtal trisomi 21, trisomi 13, trisomi 18 samt triploidi i perioden 2003 til 2013 Datasæt Region Midtjyllands database (RM) (oktober 2003 til oktober 2013); n = 147.......768. (blodprøver overvejende fra gestationsuge 8-10) Den Nationale FøtoDatabase (FD) (oktober 2008 til august 2011); n = 220.739 (blodprøver fra gestationsuge 8-13) Resultater Detektion af Trisomi 21: Første trimester ved cut off 1:300. Den signifikant bedre detektionsrate for føtal trisomi 21 ved brug af...... blodprøve i gestationsuge 9 sammenlignet med øvrige uger skyldes at PAPP-A´s diskriminationsevne er maksimal omkring gestationsuge 9. Detektion af Trisomi 18, 13 og triploidi: Tallene i parentes angiver detektionsraten efter inklusion af misdannelsesscanning i gestationsuge 18-19. Singleton (alle prøver...

  15. Complete or partial trisomy 3 in gastro-intestinal MALT lymphomas co-occurs with aberrations at 18q21 and correlates with advanced disease stage: A study on 25 cases

    Institute of Scientific and Technical Information of China (English)

    Jens Krugmann; Alexandar Tzankov; Stephan Dirnhofer; Falko Fend; Dominik Wolf; Reiner Siebert; Pensiri Probst; Martin Erdel

    2005-01-01

    @@ TO THE EDITOR Taji et al.[1] have reported in their study on 13 patients with gastric mucosa-associated lymphoid tissue (MALT) lymphomas an aggressive tumor course in trisomy 3 positive cases. The authors analyzed only stage I patients with classical low-grade marginal zone lymphoma of the MALT type and detected the trisomy 3 using an alphasatellite DNA probe directed to the centromere. Their data support the observation that trisomy 3 is the most frequent cytogenetic aberration in MALT lymphomas[2,3].

  16. A Method to Quantify Cell-Free Fetal DNA Fraction in Maternal Plasma Using Next Generation Sequencing: Its Application in Non-Invasive Prenatal Chromosomal Aneuploidy Detection

    OpenAIRE

    Xu, Xu-Ping; Gan, Hai-Yan; Li, Fen-xia; Tian, Qi; Zhang, Jun; Liang, Rong-Liang; LI Ming; Yang, Xue-Xi; Wu, Ying-Song

    2016-01-01

    Objective The fraction of circulating cell-free fetal (cff) DNA in maternal plasma is a critical parameter for aneuploidy screening with non-invasive prenatal testing, especially for those samples located in equivocal zones. We developed an approach to quantify cff DNA fractions directly with sequencing data, and increased cff DNAs by optimizing library construction procedure. Methods Artificial DNA mixture samples (360), with known cff DNA fractions, were used to develop a method to determin...

  17. The Diagnostic Significance of Comorbidities of Congenital Heart Diseases, Low-Set Ears, and Intrauterine Growth Restriction in Neonates With Trisomies 13 and 18

    Directory of Open Access Journals (Sweden)

    Yoshimitsu Fujii

    2016-06-01

    Full Text Available Background Trisomies 13 and 18 (T13/18 are autosomal trisomy syndromes with dismal prognoses. Deciding whether to perform a chromosomal analysis for the definitive diagnosis is often difficult (even for experienced pediatricians because representative clinical signs may not be found in all T13/18 neonates. Objectives This study aimed to investigate any clinical signs that could be useful for screening for T13/18 in participants without the representative clinical signs traditionally found in odd-looking neonates with malformation syndromes. Patients and Methods We retrospectively analyzed 15 T13/18 patients, 33 trisomy 21 patients, and 48 controls with other malformation syndromes, for apparent clinical signs during the neonatal period. All participants had been admitted to the neonatal intensive care unit of Kansai Medical University over a nine-year period. Results The three leading clinical signs in patients with T13/18 were congenital heart diseases (CHD; 100%, low-set ears (LSE; 80%, and intrauterine growth restriction (IUGR; 73.3%. A comorbidity of these two leading non-specific clinical signs was CHD with LSE, which showed the highest diagnostic accuracy between T13/18 and controls with a sensitivity of 80.0% and a negative predictive value of 92.5%. The chi-square test among these three groups (P < 0.01 and multiple comparison tests of proportional differences showed that the comorbidity of CHD with LSE was specific for autosomal trisomy syndromes. A comorbidity of CHD with IUGR also revealed a similar diagnostic accuracy with a sensitivity of 73.3% and a negative predictive value of 90.9% as well as a specificity for T13/18. Conclusions The comorbidities of either CHD with LSE or CHD with IUGR should be suspected in neonates with autosomal trisomy syndromes, particularly T13/18 without the expected representative clinical signs.

  18. A simple and reliable in vitro test system for the analysis of induced aneuploidy as well as other cytogenetic end-points using Chinese hamster cells

    International Nuclear Information System (INIS)

    Although aneuploidy is a serious human health problem, the experimental methodology devised until now to study the mechanisms involved in the induction of aneuploidy and for the screening of aneuploidy-inducing agents has not been so much employed to have the necessary validation. A procedure using primary cell cultures of Chinese hamster embryo cells grown on cover glasses is described. To avoid the excessive scattering and subsequent loss of chromosomes, a hypotonic treatment with a 0.17% sodium chloride solution, at room temperature, followed by in situ fixation has been standardized. This procedure improves the method through the reduction of the spontaneous frequency of aneuploid cells. Experiments carried out with cells treated with X-rays, X-rays plus caffeine, and the synthetic estrogen diethylstilbestrol (DES) demonstrated the accuracy of the system since the average chromosome number remained constant in spite of the induction of high frequencies of aneuploid cells. Moreover, the method allows for the analysis of other cytogenetic endpoints such as anaphase-telophase alterations, structural chromosome aberrations or sister chromatid exchanges. (author)

  19. Glomerular changes in trisomy 18-related horseshoe kidney: report of a case and review of the literature

    Directory of Open Access Journals (Sweden)

    Giuseppina Parodo

    2012-10-01

    Full Text Available A case of horseshoe kidney is reported in a 11 week-old fetus affected by trisomy 18. Macroscopic examination did not show any other pathological change. The histological picture of the fused-kidney was characterized by architectural and glomerular changes. At x 100 magnification, large areas of metanephric mesenchyme, characterized by spindle cells surrounded by a loose oedematous stroma, were detected in the deep cortex and in the medulla. At higher power, multiple glomerular changes were observed. Maldeveloped glomeruli showed enlarged capsular spaces, adhesions between vascular tuft and capsular cells, podocytes in multiple layers, and large glomerular bodies formed by two vascular tufts. Our data confirm previous reports on glomerular changes in horseshoe kidney, and reinforce the hypothesis that horseshoe kidney should not be considered a simple fusion problem, but a complex developmental abnormality, possibly involving glomerular development.

  20. Trisomy 12 in a Case of Multiple Cutaneous Squamous Cell Carcinoma in Association with Chronic Lymphocytic Leukemia

    Institute of Scientific and Technical Information of China (English)

    XU Zhou-min; CHEN Yan; GAO Wei-ran

    2007-01-01

    Chronic lymphocytic leukaemia (CLL), which shares clinical and morphological overlap with small lymphocytic lyjmphoma (SLL), is a low-grade clonal B-cell lymphoproliferative disorder that accounts for 25% of all cases of leukaemia in Western countries, while it is considered rare in Oriental patients and is thought to constitute only 2% of all leukemias in these patients[1]. CLL is associated with an increased incidence of secondary malignant neoplasms, such as brain tumors, melanomas, and gastrointestinal-tract carcinomas[2]. However, the simulataneous occurrence of CLL and cutaneous squamous cell carcinoma (SCC) is rarely reported. We present here a case of CLL with multiple SCC on the face. Subsequent studies demonstrated the patient to have a trisomy 12 identified in bone marrow specimen.

  1. Development of mixed connective tissue disease and Sjögren's syndrome in a patient with trisomy X.

    Science.gov (United States)

    Fujimoto, M; Ikeda, K; Nakamura, T; Iwamoto, T; Furuta, S; Nakajima, H

    2015-10-01

    Increased risk of developing systemic lupus erythematosus (SLE) has been reported in patients with Klinefelter syndrome. Here, we describe a 16-year-old Japanese patient with trisomy X (47,XXX) who developed mixed connective tissue disease (MCTD) and Sjögren's syndrome. She had polyarthritis, edematous fingers with Raynaud's phenomenon, sicca syndrome, interstitial lung disease, possible myositis, and was positive for anti-nuclear antibody, anti-nRNP antibody and rheumatoid factor. This is the first report in the literature of a case of MCTD with female polysomy X, which further supports the link between the presence of extra X chromosome(s) and the development of autoimmune diseases. PMID:25854827

  2. A rare Robertsonian translocation rob(14;22) carrier with azoospermia, meiotic defects, and testicular sperm aneuploidy.

    Science.gov (United States)

    Sobotka, Vladimir; Vozdova, Miluse; Heracek, Jiri; Rubes, Jiri

    2015-01-01

    Male infertility is a serious problem in an increasing number of couples. We report an infertile man with non-obstructive azoospermia and karyotype 45,XY,rob(14;22). The immunofluorescence analysis of his testicular tissue using antibodies to SYCP1, SYCP3, HORMAD2, MLH1, and centromeres showed delayed synapsis of the chromosomes involved in the translocation, a varying extent of trivalent asynapsis and its association with sex chromosomes. The mean frequency of meiotic recombination per cell was within the range of normal values. Fluorescence in situ hybridization (FISH) with probes for chromosomes 14 and 22 revealed 5.83% of chromosomally abnormal testicular spermatozoa. FISH with probes for chromosomes X, Y, and 21 showed frequencies of disomic and diploid testicular spermatozoa increased when compared to ejaculated sperm of healthy donors, but comparable with published results for azoospermic patients. PGD by FISH for the translocation and aneuploidy of chromosomes X, Y, 13, 18, and 21 showed a normal chromosomal complement in one out of three analyzed embryos. A healthy carrier girl was born after the embryo transfer. This study shows the benefits of preimplantation genetic diagnosis in a case of a rare Robertsonian translocation carrier with azoospermia and a relatively low frequency of chromosomally unbalanced testicular spermatozoa.

  3. DNA aneuploidy as a topographic malignant transformation pattern in a pleomorphic adenoma of long-term evolution: a case report

    Directory of Open Access Journals (Sweden)

    Gallego Lorena

    2011-11-01

    Full Text Available Abstract Introduction We present a case of long-term evolution of a submandibular pleomorphic adenoma. There is little information about topographic malignant transformation patterns of pleomorphic adenomas. Case presentation We extensively analyze a giant submandibular mixed tumor of 25-year evolution in a 57-year-old Caucasian woman. Deoxyribonucleic acid ploidy was evaluated in different superficial and deep areas using flow cytometry analysis and correlated with pathological and immunohistochemical characteristics. Superficial areas exhibited a typical histological pleomorphic adenoma pattern and were deoxyribonucleic acid diploid. Deep samples showed deoxyribonucleic acid aneuploidy, atypical histological benign features and expression of markers involved at an early-stage of malignant transformation, such as tumor protein 53 and antigen Ki67. Conclusion These findings revealed that deep tumor compartments may be involved in the initial stages of malignant transformation. Deoxyribonucleic acid ploidy analysis may provide an additional diagnosis tool and indicate 'uncertain' areas that require careful study to avoid diagnostic errors. Larger studies are needed to confirm our results and to evaluate the usefulness of the technique.

  4. Stranglehold on the spindle assembly checkpoint: the human papillomavirus E2 protein provokes BUBR1-dependent aneuploidy.

    Science.gov (United States)

    Tan, Chye Ling; Teissier, Sébastien; Gunaratne, Jayantha; Quek, Ling Shih; Bellanger, Sophie

    2015-01-01

    The Human Papillomavirus (HPV) E2 protein, which inhibits the E6 and E7 viral oncogenes, is believed to have anti-oncogenic properties. Here, we challenge this view and show that HPV-18 E2 over-activates the Spindle Assembly Checkpoint (SAC) and induces DNA breaks in mitosis followed by aneuploidy. This phenotype is associated with interaction of E2 with the Mitotic Checkpoint Complex (MCC) proteins Cdc20, MAD2 and BUBR1. While BUBR1 silencing rescues the mitotic phenotype induced by E2, p53 silencing or presence of E6/E7 (inactivating p53 and increasing BUBR1 levels respectively) both amplify it. This work pinpoints E2 as a key protein in the initiation of HPV-induced cervical cancer and identifies the SAC as a target for oncogenic pathogens. Moreover, our results suggest a role of p53 in regulating the mitotic process itself and highlight SAC over-activation in a p53-negative context as a highly pathogenic event. PMID:25789401

  5. Interrelationship between chromosome 8 aneuploidy, C-MYC amplification and increased expression in individuals from northern Brazil with gastric adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Danielle Queiroz Calcagno; Márcia Valéria Pitombeira Ferreira; Marília de Arruda Cardoso Smith; Rommel Rodríguez Burbano; Mariana Ferreira Leal; Aline Damaceno Seabra; André Salim Khayat; Elizabeth Suchi Chen; Samia Demachki; Paulo Pimentel Assump(c)(a)o; Mario Henrique Gir(a)o Faria; Silvia Helena Barem Rabenhorst

    2006-01-01

    AIM: To investigate chromosome 8 numerical aberrations, C-MYC oncogene alterations and its expression in gastric cancer and to correlate these findings with histopathological characteristics of gastric tumors.METHODS: Specimens were collected surgically from seven patients with gastric adenocarcinomas. Immunostaining for C-MYC and dual-color fluorescence in situ hybridization (FISH) for C-MYC gene and chromosome 8centromere were performed.RESULTS: All the cases showed chromosome 8 aneuploidy and C-MYC amplification, in both the diffuse and intestinal histopathological types of Lauren. No significant difference (P < 0.05) was observed between the level of chromosome 8 ploidy and the site, stage or histological type of the adenocarcinomas. C-MYC high amplification,like homogeneously stained regions (HSRs) and double minutes (DMs), was observed only in the intestinal-type.Structural rearrangement of C-MYC, like translocation,was observed only in the diffuse type. Regarding C-MYC gene, a significant difference (P < 0.05) was observed between the two histological types. The C-MYC protein was expressed in all the studied cases. In the intestinaltype the C-MYC immunoreactivity was localized only in the nucleus and in the diffuse type in the nucleus and cytoplasm.CONCLUSION: Distinct patterns of alterations between intestinal and diffuse types of gastric tumors support the hypothesis that these types follow different genetic pathways.

  6. Motivations for undertaking DNA sequencing-based non-invasive prenatal testing for fetal aneuploidy: a qualitative study with early adopter patients in Hong Kong.

    Directory of Open Access Journals (Sweden)

    Huso Yi

    Full Text Available BACKGROUND: A newly introduced cell-free fetal DNA sequencing based non-invasive prenatal testing (DNA-NIPT detects Down syndrome with sensitivity of 99% at early gestational stage without risk of miscarriage. Attention has been given to its public health implications; little is known from consumer perspectives. This qualitative study aimed to explore women's motivations for using, and perceptions of, DNA-NIPT in Hong Kong. METHODS AND FINDINGS: In-depth interviews were conducted with 45 women who had undertaken DNA-NIPT recruited by purposive sampling based on socio-demographic and clinical characteristics. The sample included 31 women identified as high-risk from serum and ultrasound based Down syndrome screening (SU-DSS. Thematic narrative analysis examined informed-decision making of the test and identified the benefits and needs. Women outlined a number of reasons for accessing DNA-NIPT: reducing the uncertainty associated with risk probability-based results from SU-DSS, undertaking DNA-NIPT as a comprehensive measure to counteract risk from childbearing especially at advanced age, perceived predictive accuracy and absence of risk of harm to fetus. Accounts of women deemed high-risk or not high-risk are distinctive in a number of respects. High-risk women accessed DNA-NIPT to get a clearer idea of their risk. This group perceived SU-DSS as an unnecessary and confusing procedure because of its varying, protocol-dependent detection rates. Those women not deemed high-risk, in contrast, undertook DNA-NIPT for psychological assurance and to reduce anxiety even after receiving the negative result from SU-DSS. CONCLUSIONS: DNA-NIPT was regarded positively by women who chose this method of screening over the routine, less expensive testing options. Given its perceived utility, health providers need to consider whether DNA-NIPT should be offered as part of universal routine care to women at high-risk for fetal aneuploidy. If this is the case, then

  7. The Mouse Brain Transcriptome by SAGE: Differences in Gene Expression between P30 Brains of the Partial Trisomy 16 Mouse Model of Down Syndrome (Ts65Dn) and Normals

    OpenAIRE

    Chrast, Roman; Scott, Hamish S.; Papasavvas, Marie Pierre; Rossier, Colette; Antonarakis, Emmanuel S.; Barras, Christine; Davisson, Muriel T.; Schmidt, Cecilia; Estivill, Xavier; Dierssen, Mara; Pritchard, Melanie; Antonarakis, Stylianos E

    2000-01-01

    Trisomy 21, or Down syndrome (DS), is the most common genetic cause of mental retardation. Changes in the neuropathology, neurochemistry, neurophysiology, and neuropharmacology of DS patients' brains indicate that there is probably abnormal development and maintenance of central nervous system structure and function. The segmental trisomy mouse (Ts65Dn) is a model of DS that shows analogous neurobehavioral defects. We have studied the global gene expression profiles of normal and Ts65Dn male ...

  8. Detection of fetal sex chromosomal aneuploidies by massively parallel sequencing of cell-free DNA in maternal plasma%孕妇血浆游离DNA高通量测序用于胎儿性染色体非整倍体检测的初步探讨

    Institute of Scientific and Technical Information of China (English)

    林颖; 蒋馥蔓; 秦岭; 马定远; 刘立夫; 陈芳; 张红云; 王威; 季修庆

    2013-01-01

    Objective To explore the clinical efficacy and practical feasibility of massively parallel sequencing (MPS) of cell-free DNA from maternal plasma for detection of sex chromosomal aneuploidies in prenatal diagnosis.Methods A total of 5540 maternal plasma samples from singleton pregnancy in the first or second trimester of pregnancy were collected from August 2011 to December 2012,and detected by using MPS.The sequencing data were compared with the human reference gene-database and statistically analyzed by informatics.The positive cases of sex chromosomal aneuploidies were advised to accept prenatal fetal chromosomal karyotype analysis of amniotic fluid cells using G-banding technique.Results In 10 of 5540 pregnant women MPS revealed sex chromosomal aneuploidies.Using the results of fetal chromosomal karyotyping as golden standard,6 of 10 cases were validated by prenatal karyotyping,including 3 cases of 45,X,1 cases of 47,XXY and 2 case of 47,XYY,while the other 4 cases were confirmed to be euploid karyotype.Conclusion MPS based on maternal plasma DNA to detect fetal sex chromosomal aneuploidies should be feasible,but there can be false positive results.The MPS technology should still be improved for detecting sex chromosomal aneuploidies.%目的 初步探讨孕妇血浆游离DNA高通量测序用于产前胎儿性染色体非整倍体检测的效果及临床可行性.方法 2011年至2012年收集早、中孕期单胎孕妇5540例,在知情同意的原则下采集外周血血浆进行游离DNA的高通量测序检测,通过生物信息学分析,获得测序结果;对测序检出的性染色体非整倍体患者行羊水穿刺,进行染色体G显带分析.结果 5540例样本中测序方法共检出10例性染色体非整倍体,其中6例与G带核型分析结果一致,包括3例45,X,1例47,XXY,2例47,XYY,其余4例G带核型正常.结论 孕母血浆游离DNA高通量测序可对性染色体非整倍体胎儿进行无创性产前检测,但存在假阳性,还需

  9. An Economic Analysis of Cell-Free DNA Non-Invasive Prenatal Testing in the US General Pregnancy Population

    OpenAIRE

    Benn, Peter; Curnow, Kirsten J.; Chapman, Steven; Michalopoulos, Steven N.; Hornberger, John; Rabinowitz, Matthew

    2015-01-01

    Objective Analyze the economic value of replacing conventional fetal aneuploidy screening approaches with non-invasive prenatal testing (NIPT) in the general pregnancy population. Methods Using decision-analysis modeling, we compared conventional screening to NIPT with cell-free DNA (cfDNA) analysis in the annual US pregnancy population. Sensitivity and specificity for fetal aneuploidies, trisomy 21, trisomy 18, trisomy 13, and monosomy X, were estimated using published data and modeling of b...

  10. Maternal Cell free DNA based screening for fetal microdeletion and the importance of careful diagnostic follow up

    OpenAIRE

    Yatsenko, Svetlana A.; Peters, David; Saller, Devereux; Chu, Tianjiao; Clemens, Michelle; Rajkovic, Aleksandar

    2015-01-01

    Background Noninvasive prenatal screening (NIPS) by next-generation sequencing of cell free DNA (cfDNA) in maternal plasma is used to screen for common aneuploidies such as trisomy 21, in high risk pregnancies. NIPS can identify fetal genomic microdeletions, however sensitivity and specificity have not been systematically evaluated. Commercial companies have begun to offer expanded panels including screening for common microdeletion syndromes such as 22q11.2 deletion (DiGeorge syndrome) witho...

  11. Sperm chromosome analysis and preimplantation genetic diagnosis in an infertile male with mosaic trisomy 18%一例嵌合型18三体少精子症患者精染色体分析及植入前遗传学诊断

    Institute of Scientific and Technical Information of China (English)

    罗玉琴; 钱羽力; 朱瑞建; 叶英辉; 朱宇宁; 金帆

    2010-01-01

    Objective To analyze the numerical aberration rate of X, Y and chromosome 18 in sperms from an oligozoospermic male with mosaic trisomy 18 and to perform preimplantation genetic diagnosis (PGD) for the couple. Methods G-banding and fluorescence in situ hybridization (FISH) were performed on metaphase chromosome. Sperm was analyzed in three-color FISH with a probe mixture containing CEP18, CEPY and Tel Xq/Yq. A healthy man with normal semen parameters was used as control. Results Significant difference in the rates of disomy for chromosome 18 (0. 63% vs. 0. 16%) and the gonosomes (0. 94% vs. 0. 35%) and diploidy (0. 87% vs. 0. 31%) was found in the spermatozoa between the patient and the control. After four embryos were biopsied in one PGD cycle, two embryos with XY1818 and XX1818 were selected for implanting and clinical pregnancy was ongoing. Conclusion SpermFISH allows further understanding of aneuploidy rate and accurate genetic counseling. FISH-PGD was effective for patient with mosaic trisomy 18.%目的 分析1例嵌合型18三体少精子患者精子18、X、Y染色体数目畸变并进行植入前遗传学诊断(preimplantation genetic djagnosis,PGD).方法 采用G带及荧光原位杂交(fluorescence in situ hybridjzation,FISH)对中期分裂相进行分析,应用三色探针CEP18、CEPY、Tel Xq/Yq对患者精子进行FISH分析,同时以1名染色体正常男性的正常精液作为对照,并对嵌合型18三体患者进行PGD.结果 患者精子18二体率、性染色体二体率和二倍体率分别为0.63%、0.94%和0.87%,与对照组相比(0.16%、0.35%、0.31%)差异有统计学意义.患者进行1个PGD周期的治疗、活检4个胚胎,移植正常的XY1818、XX1818各1胚胎后获得临床妊娠.结论 精子FISH分析可为其提供更准确的遗传咨询及指导植入前遗传学诊断,FISH-PGD可有效地应用于嵌合型18三体的植入前遗传学诊断.

  12. Trisomy 8p (p11.2-pter due to maternal translocation t(8;13(p11;p12 in a child with dysmorphic features

    Directory of Open Access Journals (Sweden)

    Mahjoubi F

    2005-01-01

    Full Text Available Here we present a phenotypic description of a male child with trisomy 8p resulting from a maternal balanced reciprocal translocation. The patient presented with dysmorphic face, aplasia of the corpus callosum, and atrophy of cortex, congenital heart defect and marked hypotonia. The father had a normal karyotype. The mother had an apparently balanced translocation involving chromosomes 8 and 13 [46, XX, t(8;13(p11.2;p12]. The karyotype of the child was ascertained as 46, XY, der(13t(8;13(p11.2;p12. This is the second reported case of trisomy 8p resulting from a translocation between chromosomes 8 and 13. The chromosomal breakpoints in the two cases differed.

  13. Management of the Difficult Paediatric Airway with a Simple Fiberoptic-Assisted Laryngoscope: A Report of Two Cases with Pierre Robin and Patau’s (Trisomy 13) Syndrome

    OpenAIRE

    Kılıçaslan, Alper; Erol, Atilla; Topal, Ahmet; Et, Tayfun; Otelcioğlu, Şeref

    2014-01-01

    Airway management of children with congenital craniofacial anomalies is a challenge for paediatric anaesthesiologists. We do not have any video-assisted airway device in our department for difficult paediatric intubations. We decided to attach a regular fiberoptic (outer diameter; 3.7 mm, Karl Storz, Germany) scope to a conventional Macintosh Laryngoscope (size 1). We describe two cases of Pierre Robin and Patau’s (Trisomy 13) syndrome successfully intubated with a fiberoptic-assisted laryngo...

  14. Pure partial trisomy of 6p12.1-p22.1 secondary to a familial 12/6 insertion in two malformed babies.

    Science.gov (United States)

    Fogu, Giuseppina; Bandiera, Pasquale; Cambosu, Francesca; Carta, Anna Rita; Pilo, Laura; Serra, Gigliola; Soro, Giovanna; Tondi, Massimo; Tusacciu, Gianni; Montella, Andrea

    2007-01-01

    We describe two malformed infants with trisomy 6p12.1-p22.1 due to 12/6 interchromosomal insertion. The phenotypic data observed in these patients are compared chiefly with a case cytogenetically similar described by Villa et al. [A. Villa, E.G. Gomez, L. Rodriguez, R.H. Rastrollo, M.E. Martinez Tallo, M.L. Martinez-Frias, Interstitial tandem duplication of 6p: a case with partial trisomy (6)(p12p21.3), Am. J. Med. Genet. 90 (2000) 369-375]. All three infants are trisomic for a genomic segment which largely overlaps that reported as duplicated in previous cases, but with the addition of a more proximal segment, extending from 6p12 to 6p21. We suggest that some of their phenotypic anomalies are due to the trisomy of this chromosomal region. We also speculate on the possible role played by the TFAP2B (Transcription Factor AP2-beta) gene, which is one of the genes mapped on the duplicated segment. PMID:17185054

  15. Papillary Thyroid Cancer in Struma Testis with Malignant Transformation in the Lung Associated with Trisomy 17 Successfully Treated with Total Thyroidectomy and Radioiodine Ablation

    Directory of Open Access Journals (Sweden)

    Shadi Barakat

    2014-11-01

    Full Text Available Background: Struma testis is a rare entity, and there are only few reports on the malignant transformation of a testicular teratoma to papillary thyroid carcinoma in the literature. In this report, we describe the malignant transformation of struma testis with distant lung metastasis associated with trisomy 17 and a coexisting papillary microcarcinoma in the thyroid. Case Report: A 56-year-old man presented after a left orchiectomy for an undescended left testicle. Pathologic examination identified a monodermal teratoma composed of thyroid parenchyma and associated with a 1.7-cm papillary thyroid carcinoma. Further evaluation showed a pulmonary mass on a chest CT scan. Total thyroidectomy revealed a 0.5-mm focus of papillary thyroid cancer, and removal of the lung mass confirmed metastatic papillary thyroid cancer. Array-comparative genomic hybridization of both tumors showed trisomy 17 in the struma testes and the lung metastasis. The patient responded well to radioactive iodine ablation and has no evidence of cancer 3 years later. Conclusion: To our knowledge, this is the first case of papillary thyroid cancer in struma testes metastatic to the lung. It highlights the difficulties in treating these patients. Surgery to remove cancer foci, followed by radioactive iodine ablation, resulted in an excellent response in our patient. Interestingly, trisomy 17, which has so far been observed only in noninvasive thyroid nodules, was associated with pulmonary metastasis in our patient.

  16. A dominant negative mutant of TLK1 causes chromosome missegregation and aneuploidy in normal breast epithelial cells

    Directory of Open Access Journals (Sweden)

    Williams Briana

    2003-10-01

    Full Text Available Abstract Background In Arabidopsis thaliana, the gene Tousled encodes a protein kinase of unknown function, but mutations in the gene lead to flowering and leaf morphology defects. We have recently cloned a mammalian Tousled-Like Kinase (TLK1B and found that it phosphorylates specifically histone H3, in vitro and in vivo. We now report the effects that overexpression of a kinase-dead mutant of TLK1B mediates in a normal diploid cell line. Results Expression of a kinase-dead mutant resulted in reduction of phosphorylated histone H3, which could have consequences in mitotic segregation of chromosomes. When analyzed by FACS and microscopy, these cells displayed high chromosome number instability and aneuploidy. This phenomenon was accompanied by less condensed chromosomes at mitosis; failure of a number of chromosomes to align properly on the metaphase plate; failure of some chromosomes to attach to microtubules; and the occasional presentation of two bipolar spindles. We also used a different method (siRNA to reduce the level of endogenous TLK1, but in this case, the main result was a strong block of cell cycle progression suggesting that TLK1 may also play a role in progression from G1. This block in S phase progression could also offer a different explanation of some of the later mitotic defects. Conclusions TLK1 has a function important for proper chromosome segregation and maintenance of diploid cells at mitosis in mammalian cells that could be mediated by reduced phosphorylation of histone H3 and condensation of chromosomes, although other explanations to the phenotype are possible.

  17. Investigation of ultrasound markers in screening fetal trisomy 21%超声软指标在筛查胎儿21三体综合征中的应用

    Institute of Scientific and Technical Information of China (English)

    石晓梅; 方群; 陈宝江; 谢红宁; 谢英俊; 陈筠虹; 吴坚柱

    2013-01-01

    Objective To investigate the clinical value of ultrasound markers in screening fetal trisomy 21.Methods From Jan.2001 to Dec.2011,a retrospective study about sonographic information of 138 fetuses diagnosed as trisomy 21 was taken in the First Affiliated Hospital of Sun Yat-sen University.All fetuses were divided into 3 groups:isolated ultrasound markers,non-isolated ultrasound markers,and isolated structural malformations or other abnormalities.The relationship between trisomy 21 and ultrasound markers as well as structural anomalies or other abnormalities was analyzed.Results Sonographic anomalies were detected in 132 fetuses(95.7%,132/138),including ultrasound markers and structural malformations or other abnormalities.One hundred and twenty cases(87.0%,120/138)had ultrasound markers,38(31.7%,38/120)had one marker and 82(68.3%,82/120)had more than one marker (P < 0.01).Fifty-one fetuses(37.0%,51/138)had isolated ultrasound markers and non-isolated markers were found in 69 fetuses(50.0%,69/138).Only 12 fetuses(8.7%,12/138)had isolated structural malformations or other abnormalities.In 20 fetuses on whom the first-trimester ultrasound screening were performed,all had ultrasound markers,95%(19/20)had thickened nuchal translucency and 55% (11/20)had nasal bone hypoplasia.The most common ultrasound markers on the second-trimester screening were nasal bone hypoplasia,which accounted for 41.9%(52/124)cases,followed by thickened nuchal fold (25.0%,31/124),short fenurs and humerus(24.2%,30/124),echogenic intracardiac focus(16.1%,20/124),mild ventriculomegaly(15.3%,19/124),hyperechoic bowel(12.9%,16/124),mild renal pyelectasis(12.1%,15/124).Furthermore,thc common structural malformations or other abnormalities were as follows:cardiac defects(33.1%,41/124),digestive system(26.6%,33/124).Condusions Ultrasound markers are valuable for screening fetal trisomy 21.The fetuses of trisomy 21 usually had more than one ultrasound markers or

  18. Application of next-generation DNA sequencing for prenatal testing of fetal chromosomal aneuploidies%新一代测序技术用于胎儿染色体非整倍体无创产前检测的研究

    Institute of Scientific and Technical Information of China (English)

    刘静; 王华; 席惠; 贾政军; 周玉春; 邬玲仟

    2015-01-01

    Objective To explore the value of next-generation sequencing for the non-invasive prenatal testing of fetal chromosomal aneuploidies.Methods Plasma from 4004 women with singleton pregnancy at a gestational age between 12~35+5 weeks was collected prior to amniocentesis between April 19th 2011 and December 31st 2013.The samples were divided into three groups:(1) High risk for Down syndrome by biochemical screening;(2) Advanced maternal age;(3) Abnormalities by ultrasound or other methods.Plasma DNA extracted from above samples was sequenced at low coverage.Positive results were verified against the karyotypes of the fetuses.For those with negative results,the fetuses were followed up by telephone call for at least six months after birth.Results Among 4003 samples subjected to non-invasive prenatal diagnosis,66 (1.65%) had a positive result.In group 1,22 cases of trisomy 21 (T21),3 cases of risomy 18 (T18),1 case of 13 trisomy (T13),8 cases of 45,X and 2 cases of other chromosomal abnormality were detected.In group 2,13 cases of T21,2 cases of T18,1 case of T13,5 cases of 45,X,2 cases of 47,XXN and 1 case of other chromosomal abnormality were detected.In group 3,1 case of T21,1 case of T18,1 case of T13,and 3 cases of 47,XXN were detected.For 55 samples underwent prenatal diagnosis,30 cases of T21 and 4 cases of T18 were discovered,which was consistent with the results of noninvasive prenatal diagnosis.For the 13 cases indicated as 45,X,3 were verified by karyotype analysis,2 were verified as mosaicism (45,X/46,XN),8 were 46,XN (false positives).For the 5 cases indicated as 47,XXN,2 were verified by karyotype analysis,the other 3 were 46,XN (false positives).Karyotypes of 3 cases suspected for other chromosomal abnormalities were all verified as 46,XN (false positive).Until May 1st 2014,telephone follow-up for those with negative screening results only identified a boy with facial abnormalities and developmental delay,which was similar to his older sister

  19. Optical modulator including grapene

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Ming; Yin, Xiaobo; Zhang, Xiang

    2016-06-07

    The present invention provides for a one or more layer graphene optical modulator. In a first exemplary embodiment the optical modulator includes an optical waveguide, a nanoscale oxide spacer adjacent to a working region of the waveguide, and a monolayer graphene sheet adjacent to the spacer. In a second exemplary embodiment, the optical modulator includes at least one pair of active media, where the pair includes an oxide spacer, a first monolayer graphene sheet adjacent to a first side of the spacer, and a second monolayer graphene sheet adjacent to a second side of the spacer, and at least one optical waveguide adjacent to the pair.

  20. Rapid mechanisms for generating genome diversity: whole ploidy shifts, aneuploidy, and loss of heterozygosity.

    Science.gov (United States)

    Bennett, Richard J; Forche, Anja; Berman, Judith

    2014-10-01

    Human fungal pathogens can exist in a variety of ploidy states, including euploid and aneuploid forms. Ploidy change has a major impact on phenotypic properties, including the regulation of interactions with the human host. In addition, the rapid emergence of drug-resistant isolates is often associated with the formation of specific supernumerary chromosomes. Pathogens such as Candida albicans and Cryptococcus neoformans appear particularly well adapted for propagation in multiple ploidy states with novel pathways driving ploidy variation. In both species, heterozygous cells also readily undergo loss of heterozygosity (LOH), leading to additional phenotypic changes such as altered drug resistance. Here, we examine the sexual and parasexual cycles that drive ploidy variation in human fungal pathogens and discuss ploidy and LOH events with respect to their far-reaching roles in fungal adaptation and pathogenesis. PMID:25081629