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Sample records for aneuploidy including trisomy

  1. 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.

  2. 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

  3. Trisomy 21 and Facial Developmental Instability

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    Starbuck, John M; Cole, Theodore M; Reeves, Roger H.; Richtsmeier, Joan T.

    2013-01-01

    The most common live-born human aneuploidy is trisomy 21, which causes Down syndrome (DS). Dosage imbalance of genes on chromosome 21 (Hsa21) affects complex gene-regulatory interactions and alters development to produce a wide range of phenotypes, including characteristic facial dysmorphology. Little is known about how trisomy 21 alters craniofacial morphogenesis to create this characteristic appearance. Proponents of the “amplified developmental instability” hypothesis argue that trisomy 21...

  4. Segmental trisomy of chromosome 17: a mouse model of human aneuploidy syndromes

    Czech Academy of Sciences Publication Activity Database

    Vacík, Tomáš; Ort, Michael; Gregorová, Soňa; Strnad, P.; Conte, N.; Bradley, A.; Blatný, Radek; Bureš, Jan; Forejt, Jiří

    2005-01-01

    Roč. 102, č. 12 (2005), s. 4500-4505. ISSN 0027-8424 R&D Projects: GA ČR(CZ) GA309/03/0715 Grant ostatní: Howard Hughes Medical Institute(US) 55000306 Institutional research plan: CEZ:AV0Z5011922; CEZ:AV0Z50110509 Keywords : dosage-sensitive genes * Down's syndrome * mouse segmental trisomy Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 10.231, year: 2005

  5. Trisomy 13

    Science.gov (United States)

    ... 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 ...

  6. 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.

  7. 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.

  8. 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

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

    Science.gov (United States)

    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

  10. 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, Charlotte Kvist; Petersen, Olav Bjørn; Sundberg, Karin Milner; Pedersen, Frank Henning; Vogel, Ida; Tabor, Ann

    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....

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. Trisomy 21 and facial developmental instability.

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    Starbuck, John M; Cole, Theodore M; Reeves, Roger H; Richtsmeier, Joan T

    2013-05-01

    The most common live-born human aneuploidy is trisomy 21, which causes Down syndrome (DS). Dosage imbalance of genes on chromosome 21 (Hsa21) affects complex gene-regulatory interactions and alters development to produce a wide range of phenotypes, including characteristic facial dysmorphology. Little is known about how trisomy 21 alters craniofacial morphogenesis to create this characteristic appearance. Proponents of the "amplified developmental instability" hypothesis argue that trisomy 21 causes a generalized genetic imbalance that disrupts evolutionarily conserved developmental pathways by decreasing developmental homeostasis and precision throughout development. Based on this model, we test the hypothesis that DS faces exhibit increased developmental instability relative to euploid individuals. Developmental instability was assessed by a statistical analysis of fluctuating asymmetry. We compared the magnitude and patterns of fluctuating asymmetry among siblings using three-dimensional coordinate locations of 20 anatomic landmarks collected from facial surface reconstructions in four age-matched samples ranging from 4 to 12 years: (1) DS individuals (n = 55); (2) biological siblings of DS individuals (n = 55); 3) and 4) two samples of typically developing individuals (n = 55 for each sample), who are euploid siblings and age-matched to the DS individuals and their euploid siblings (samples 1 and 2). Identification in the DS sample of facial prominences exhibiting increased fluctuating asymmetry during facial morphogenesis provides evidence for increased developmental instability in DS faces. We found the highest developmental instability in facial structures derived from the mandibular prominence and lowest in facial regions derived from the frontal prominence. PMID:23505010

  17. 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.

  18. 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

  19. Congenital anomalies associated with trisomy 18 or trisomy 13

    DEFF Research Database (Denmark)

    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

    terminations of pregnancy for fetal anomaly (TOPFAs). The prevalence of associated anomalies was reported in live births. The prevalence of trisomy 18 and trisomy 13 were 4.8 (95%CI: 4.7-5.0) and 1.9 (95%CI: 1.8-2.0) per 10,000 total births. Seventy three percent of cases with trisomy 18 or trisomy 13 resulted......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...

  20. 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

  1. 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.

  2. 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.

  3. 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...

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

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    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.

  5. Non-invasive prenatal aneuploidy testing at chromosomes 13, 18, 21, X, and Y, using targeted sequencing of polymorphic loci

    Science.gov (United States)

    Zimmermann, Bernhard; Hill, Matthew; Gemelos, George; Demko, Zachary; Banjevic, Milena; Baner, Johan; Ryan, Allison; Sigurjonsson, Styrmir; Chopra, Nikhil; Dodd, Michael; Levy, Brynn; Rabinowitz, Matthew

    2012-01-01

    Objective Develop a non-invasive prenatal test based on analysis of cell-free DNA in maternal blood to detect fetal aneuploidy at chromosomes 13, 18, 21, X, and Y. Methods 166 samples from pregnant women, including eleven trisomy 21, three trisomy 18, two trisomy 13, two 45,X, and two 47,XXY samples were analyzed using an informatics-based method. Cell-free DNA from maternal blood was isolated and amplified using a multiplex PCR assay targeting 11,000 SNPs on chromosomes 13, 18, 21, X, and Y in a single reaction, then sequenced. A Bayesian-based Maximum Likelihood statistical method was applied to determine the chromosomal count of the five chromosomes interrogated in each sample, along with a sample-specific calculated accuracy for each test result. Results The algorithm correctly reported the chromosome copy number at all five chromosomes in 145 samples that passed a DNA quality test, for a total of 725/725 correct calls. The average calculated accuracy for these samples was 99.92%. Twenty-one samples did not pass the DNA quality test. Conclusions This informatics-based method non-invasively detected fetuses with trisomy 13, 18, and 21, 45,X, and 47,XXY with high sample-specific calculated accuracies for each individual chromosome and across all five chromosomes. PMID:23108718

  6. 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.

  7. 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

  8. 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

  9. Trisomy 13 (Patau Syndrome

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    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

  10. 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

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

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    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

  12. 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.

  13. 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

  14. 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

    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 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

  15. 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

  16. 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...

  17. Trisomy 18

    Science.gov (United States)

    ... may also show kidney problems, including: Horseshoe kidney Hydronephrosis Polycystic kidney ... Tests can be done during pregnancy to find out if the child has this syndrome. Genetic testing is recommended for parents who have a child with this ...

  18. 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

  19. Radiation- induced aneuploidy in mammalian germ cells

    International Nuclear Information System (INIS)

    The ability of ionizing radiation to induce aneuploidy in mammalian germ cells has been investigated experimentally in the laboratory mouse using a variety of cytogenetic and genetic methods. These studies have provided unambiguous evidence of induced nondisjunction in both male and female germ cells when the effect of irradiation is screened in meiotic cells or preimplantation embryos. In contrast, however, cytogenetic analyses of post-implantation embryos and genetic assays for induced chromosome gains have not found a significant radiation effect. These apparently contradictory findings may be reconciled if (a) radiation induces tertiary rather than primary trisomy, or (b) induces embryo-lethal genetic damage, such as deletions, in addition to numerical anomalies. Either or both of these explanations may account for the apparent loss during gestation of radiation-induced trisomic embryos. Extrapolating from the information so far available, it seems unlikely that environmental exposure to low doses if low dose rate radiation will result in a detectable increase in the rate of aneuploidy in the human population. (author)

  20. 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...

  1. 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

  2. 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

  3. 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.

  4. 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

  5. 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...

  6. 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.

  7. 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...... for føtal aneuploidi. Brug af blodprøve fra gestationsuge 9 viser signifikant højere detektionsrate for føtal trisomi 21 end ved brug af blodprøve senere...

  8. Expanding the phenotype of mosaic trisomy 20.

    Science.gov (United States)

    Willis, Mary J H; Bird, Lynne M; Dell'Aquilla, Marie; Jones, Marilyn C

    2008-02-01

    Mosaic trisomy 20 is one of the more common cytogenetic abnormalities found on amniocentesis or chorionic villus sampling. Studies have shown that outcome is normal in 90-93% of prenatally diagnosed cases. There are however, reports in the literature of children with mosaic trisomy 20 described as having an assortment of dysmorphic features and varying levels of developmental delay. Unfortunately, the literature has not defined a specific phenotype for this entity. Here we report on three patients with mosaic trisomy 20, two of whom were identified prenatally. Over a number of years of follow-up it has become apparent that there are some striking similarities among the three. Comparison between our patients and the literature cases indicates a more consistent phenotype than has previously been suggested. Recurring features include; spinal abnormalities (including spinal stenosis, vertebral fusion, and kyphosis), hypotonia, lifelong constipation, sloped shoulders, and significant learning disabilities despite normal intelligence. These findings may be overlooked on routine history and physical exam or assumed to be standard pediatric problems. It is not our intention to suggest that there is a distinctive face for this entity but to suggest that a subtle phenotype does exist. We have attempted to identify a set of findings for which any child diagnosed with mosaic trisomy 20 should be assessed or followed even in the presence of an apparently normal physical exam at birth. PMID:18203170

  9. Trisomy 18 in a 13 year old girl.

    OpenAIRE

    Mehta, L.; Shannon, R S; Duckett, D P; Young, I D

    1986-01-01

    A 13 year old girl with trisomy 18 is described. She showed profound mental and growth retardation, severe kyphoscoliosis, and unusual ocular features including discontinuous eyebrows, distichiasis, and blue sclerae.

  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. 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.

  14. 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.

  15. 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.

  16. 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...

  17. 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.

  18. 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

  19. 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.

  20. 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 ...

  1. Methods for genetic linkage analysis using trisomies

    Energy Technology Data Exchange (ETDEWEB)

    Feingold, E. [Emory Univ. School of Public Health, Atlanta, GA (United States); Lamb, N.E.; Sherman, S.L. [Emory Univ., Atlanta, GA (United States)

    1995-02-01

    Certain genetic disorders are rare in the general population, but more common in individuals with specific trisomies. Examples of this include leukemia and duodenal atresia in trisomy 21. This paper presents a linkage analysis method for using trisomic individuals to map genes for such traits. It is based on a very general gene-specific dosage model that posits that the trait is caused by specific effects of different alleles at one or a few loci and that duplicate copies of {open_quotes}susceptibility{close_quotes} alleles inherited from the nondisjoining parent give increased likelihood of having the trait. Our mapping method is similar to identity-by-descent-based mapping methods using affected relative pairs and also to methods for mapping recessive traits using inbred individuals by looking for markers with greater than expected homozygosity by descent. In the trisomy case, one would take trisomic individuals and look for markers with greater than expected homozygosity in the chromosomes inherited from the nondisjoining parent. We present statistical methods for performing such a linkage analysis, including a test for linkage to a marker, a method for estimating the distance from the marker to the trait gene, a confidence interval for that distance, and methods for computing power and sample sizes. We also resolve some practical issues involved in implementing the methods, including how to use partially informative markers and how to test candidate genes. 20 refs., 5 figs., 1 tab.

  2. 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

  3. 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.

  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. PMID:27313317

  5. 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

  6. 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...

  7. 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)...

  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. 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

  10. 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

  11. Chest radiographic diagnosis of trisomy-21 in newborn infants

    International Nuclear Information System (INIS)

    Common chest radiographic findings in trisomy-21 include multiple manubrial ossification centers (MMC), 11 rib pairs (11R), and a notably bell-shaped chest (BSC). These findings were compared in a sequential series of 881 newborns (first 48 hours of life) without chromosomal abnormalities and 30 newborns with trisomy-21. Logistic regression analysis indicates that the probability of trisomy-21 is 0.05% when none of these findings is present, 1.6% with MMC alone, 0.2% with 11R alone, 0.7% with BSC alone, 8.8% with MMC and 11R, 19.4% with MMC and BSC, 3.9% with 11R and BSC, and 58.4% if all three findings are present

  12. 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

  13. Methods for genetic linkage analysis using trisomies

    Energy Technology Data Exchange (ETDEWEB)

    Feingold, E.; Lamb, N.E.; Sherman, S.L. [Emory Univ., Atlanta, GA (United States)

    1994-09-01

    Certain genetic disorders (e.g. congenital cataracts, duodenal atresia) are rare in the general population, but more common in people with Down`s syndrome. We present a method for using individuals with trisomy 21 to map genes for such traits. Our methods are analogous to methods for mapping autosomal dominant traits using affected relative pairs by looking for markers with greater than expected identity-by-descent. In the trisomy case, one would take trisomic individuals and look for markers with greater than expected reduction to homozygosity in the chromosomes inherited form the non-disjoining parent. We present statistical methods for performing such a linkage analysis, including a test for linkage to a marker, a method for estimating the distance from the marker to the gene, a confidence interval for that distance, and methods for computing power and sample sizes. The methods are described in the context of gene-dosage model for the etiology of the disorder, but can be extended to other models. We also resolve some practical issues involved in implementing the methods, including how to use partially informative markers, how to test candidate genes, and how to handle the effect of reduced recombination associated with maternal meiosis I non-disjunction.

  14. 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.

  15. 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.

  16. 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

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

    OpenAIRE

    Shu, X.; Zou, C; Shen, Z

    2013-01-01

    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...

  18. 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

  19. Aneuploidy in mammalian somatic cells in vivo.

    Science.gov (United States)

    Cimino, M C; Tice, R R; Liang, J C

    1986-01-01

    Aneuploidy is an important potential source of human disease and of reproductive failure. Nevertheless, the ability of chemical agents to induce aneuploidy has been investigated only sporadically in intact (whole-animal) mammalian systems. A search of the available literature from the EMCT Aneuploidy File (for years 1970-1983) provided 112 papers that dealt with aneuploidy in mammalian somatic cells in vivo. 59 of these papers did not meet minimal criteria for analysis and were rejected from subsequent review. Of the remaining 53 papers that dealt with aneuploidy induction by chemical agents in mammalian somatic cells in vivo, only 3 (6%) contained data that were considered to be supported conclusively by adequate study designs, execution, and reporting. These 3 papers dealt with 2 chemicals, one of which, mercury, was negative for aneuploidy induction in humans, and the other, pyrimethamine, was positive in an experimental rodent study. The majority of papers (94%) were considered inconclusive for a variety of reasons. The most common reasons for calling a study inconclusive were (a) combining data on hyperploidy with those on hypoploidy and/or polyploidy, (b) an inadequate or unspecified number of animals and/or cells per animal scored per treatment group, and (c) poor data presentation such that animal-to-animal variability could not be assessed. Suggestions for protocol development are made, and the future directions of research into aneuploidy induction are discussed. PMID:3941670

  20. Klinefelter syndrome and other sex chromosomal aneuploidies

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    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

  1. 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.

  2. Trisomy 15 mosaicism in an IVF fetus.

    OpenAIRE

    Bennett, C P; T. Davis; Seller, M J

    1992-01-01

    Prenatal diagnosis of an IVF pregnancy in a woman aged 41 years showed a fetus mosaic for trisomy 15. The fetus had dysmorphic features, hypoplastic adrenal glands, and an accessory spleen. Both IVF and advanced maternal age would seem to increase the risk of trisomy 15.

  3. 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

  4. 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

  5. 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

  6. 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,...

  7. 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

  8. 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.

  9. 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

  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. SNP microarray-based 24 chromosome aneuploidy screening demonstrates that cleavage-stage FISH poorly predicts aneuploidy in embryos that develop to morphologically normal blastocysts.

    Science.gov (United States)

    Northrop, L E; Treff, N R; Levy, B; Scott, R T

    2010-08-01

    Although selection of chromosomally normal embryos has the potential to improve outcomes for patients undergoing IVF, the clinical impact of aneuploidy screening by fluorescence in situ hybridization (FISH) has been controversial. There are many putative explanations including sampling error due to mosaicism, negative impact of biopsy, a lack of comprehensive chromosome screening, the possibility of embryo self-correction and poor predictive value of the technology itself. Direct analysis of the negative predictive value of FISH-based aneuploidy screening for an embryo's reproductive potential has not been performed. Although previous studies have found that cleavage-stage FISH is poorly predictive of aneuploidy in morphologically normal blastocysts, putative explanations have not been investigated. The present study used a single nucleotide polymorphism (SNP) microarray-based 24 chromosome aneuploidy screening technology to re-evaluate morphologically normal blastocysts that were diagnosed as aneuploid by FISH at the cleavage stage. Mosaicism and preferential segregation of aneuploidy to the trophectoderm (TE) were evaluated by characterization of multiple sections of the blastocyst. SNP microarray technology also provided the first opportunity to evaluate self-correction mechanisms involving extrusion or duplication of aneuploid chromosomes resulting in uniparental disomy (UPD). Of all blastocysts evaluated (n = 50), 58% were euploid in all sections despite an aneuploid FISH result. Aneuploid blastocysts displayed no evidence of preferential segregation of abnormalities to the TE. In addition, extrusion or duplication of aneuploid chromosomes resulting in UPD did not occur. These findings support the conclusion that cleavage-stage FISH technology is poorly predictive of aneuploidy in morphologically normal blastocysts. PMID:20479065

  12. 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.

  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. 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.

  16. 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、

  17. 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.

  18. 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

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

    Science.gov (United States)

    El Khattabi, Laïla Allach; Rouillac-Le Sciellour, Christelle; Le Tessier, Dominique; Luscan, Armelle; Coustier, Audrey; Porcher, Raphael; Bhouri, Rakia; Nectoux, Juliette; Sérazin, Valérie; Quibel, Thibaut; Mandelbrot, Laurent; Tsatsaris, Vassilis

    2016-01-01

    Objective 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. Method 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. Results 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. Conclusion 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. PMID:27167625

  20. 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.

  1. Histogenesis of retinal dysplasia in trisomy 13

    Directory of Open Access Journals (Sweden)

    Gonzalez-Fernandez Federico

    2007-12-01

    Full Text Available 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 structures. A detailed histopathological study of the ocular structures was performed. The expression of interphotoreceptor retinoid-binding protein (IRBP, cellular retinal-binding protein (CRALBP, rod opsin, and Sonic Hedgehog (Shh were studied by immunohistochemistry. Results Holoprosencephaly, and a spectrum of anatomical findings characteristic of Patau's syndrome, were found. Cytogenetic studies demonstrated trisomy 13 [47, XY, +13]. The eyes were fused but contained two developed separate lenses. In contrast, the cornea, and angle structures were hypoplastic, and the anterior chamber had failed to form. The retina showed areas of normally laminated neural retina, whereas in other areas it was replaced by numerous neuronal rosettes. Histological and immunohistochemical studies revealed that the rosettes were composed of differentiated retinal neurons and Müller cell glia. In normally laminated retina, Shh expression was restricted to retinal-ganglion cells, and to a population of neurons in the inner zone of the outer nuclear layer. In contrast, Shh could not be detected in the dysplastic rosettes. Conclusion The histopathology of cyclopia appears to be more complex than what may have been previously appreciated. In fact, the terms "cyclopia" and "synophthalmia" are misnomers as the underlying mechanism is a failure of the eyes to form separately during development. The rosettes found in the dysplastic retina are fundamentally different than those of

  2. 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

  3. 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...

  4. 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

  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. Frequency of trisomy 21 in Germany before and after the Chernobyl accident

    International Nuclear Information System (INIS)

    For Berlin (West) the rate of trisomy 21 among newborn and all prenatally diagnosed cases can be almost completely recorded, including the maternal age distribution. During the 9-year-period from 1980 to 1988 the average number of trisomy 21 per month was about 2, following a Poisson distribution. A significant increase (P 30 000 prenatal diagnoses performed in 1986, no significant effect could be observed. However, the highest rates of trisomy 21 were observed in the more heavily contaminated, southern part of Germany. The majority of these fetuses were conceived during the period of greatest radioactive exposure. The data are discussed with respect to the effect of low-dose radiation around the time of conception on the induction of non-disjunction in man

  8. A case of trisomy of chromosome 15

    OpenAIRE

    Coldwell, S; Fitzgerald, B.; Semmens, J.M.; Ede, R; Bateman, C

    1981-01-01

    We describe a case of trisomy of chromosome 15 in an infant who presented at birth with numerous abnormalities. As far as we are aware this chromosomal abnormality has not been described before. On the basis of this one case there appear to be no features which are specific to this chromosomal abnormality.

  9. Fertility in a male with trisomy 21.

    Science.gov (United States)

    Sheridan, R; Llerena, J; Matkins, S; Debenham, P; Cawood, A; Bobrow, M

    1989-01-01

    We review the published reports on reproduction in cases of non-mosaic trisomy 21 (Down's syndrome) and present the first fully documented case of a non-mosaic male with Down's syndrome fathering a pregnancy, a fact which has important implications in the light of caring for these people in the community. Images PMID:2567354

  10. 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

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

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    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

  12. 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

  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. 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.

  15. 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

  16. 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.

  17. 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...

  18. 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...

  19. Clinical impact of aneuploidy on gastric cancer patients.

    Science.gov (United States)

    Sánchez-Pérez, Isabel; García Alonso, Pilar; Belda Iniesta, Cristóbal

    2009-08-01

    Gastric cancer is a leading cause of death worldwide. Nowadays, complete surgical resection and TNM at diagnosis are the main prognostic factors. In spite of this, many patients will have a recurrence after surgery and die within a few months or years. That means that we need more accurate prognostic factors to design specific approaches for individual patients. Chromosome instability is a feature of gastric cancer commonly associated to chromosomal aberrations that leads to major modifications of DNA content globally termed as aneuploidy. In this regard, many authors' opinions diverge regarding the clinical impact of aneuploidy. This review will summarise data on the clinical impact of aneuploidy on clinical practice, the biological mechanisms that underlie chromosomal instability that induces aneuploidy and the relevance of specific chromosomal aneuploidy to cancer biology. PMID:19661021

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. Trisomy 13 in monozygotic twins discordant for major congenital anomalies.

    OpenAIRE

    Naor, N; Amir, Y; Cohen, T; Davidson, S.

    1987-01-01

    The occurrence of trisomy 13 in twins is very rare. We report a pair of genotypically identical twins with trisomy 13 discordant for major anomalies. This case contributes to the already published data on the contribution of non-genetic factors to the aetiology of congenital malformations in monozygotic twins.

  6. Congenital Ocular Anomaly in an Infant with Trisomy 14 Mosaicism

    OpenAIRE

    Choi, Jun Ho; Choi, Youn Joo; Kim, So Young

    2012-01-01

    Trisomy 14 mosaicism is a rare chromosomal abnormality with distinct and recognizable clinical features. We report a patient with presumed retinal dystrophy having diffuse retinal pigment epithelial abnormalities, which has not been previously reported in association with trisomy 14. This case expands the clinical spectrum of this rare entity.

  7. Stable Variants of Sperm Aneuploidy among Healthy Men Show Associations between Germinal and Somatic Aneuploidy

    Czech Academy of Sciences Publication Activity Database

    Rubeš, Jiří; Vozdová, M.; Robbins, W. A.; Řezáčová, O.; Perreault, S. D.; Wyrobek, A. J.

    2002-01-01

    Roč. 70, - (2002), s. 1507-1519. ISSN 0002-9297 R&D Projects: GA MŽP SI/340/1/97 Grant ostatní: GA-(US) 98-NCERQA-C1 Institutional research plan: CEZ:AV0Z5039906 Keywords : Human sperm quality * aneuploidy * reproductive health Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 10.649, year: 2002

  8. 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...

  9. 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 ...... our study is that the total palatal length in prenatal trisomy 21 is shorter than normal and that this is due both to a shortness of the maxillary and the palatine components of the hard palate....

  10. 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.

  11. 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…

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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...

  18. 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

  19. 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

  20. 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

  1. 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.

  2. Mouse trisomy 16: An animal model of human trisomy 21 (Down syndrome)

    International Nuclear Information System (INIS)

    One of the principal difficulties in studying human disorders of development, particularly if the nervous system is involved, is our inability for both technical and ethical reasons to study more than a very restricted number of tissues and developmental processes. The developing human fetus is inaccessible to any type of systematic study, and the brain can only be approached postmortem or, during life, by a limited number of noninvasive techniques. Whereas the latter methods, particularly positron emission tomography and nuclear magnetic resonance spectroscopy, are beginning to be applied to the study of central nervous system metabolism, their view of the details of nervous system function is still limited. Therefore, to study the mechanisms underlying the development of abnormalities associated with a condition such as trisomy 21, abnormalities both of prenatal somatic and neurologic development, and probably neurologic development and function as well, it is necessary to have experimental systems that lend themselves to convenient analysis. To accomplish this the authors sought to develop an animal model for human trisomy 21 and its phenotypic representation, Down syndrome

  3. 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

  4. 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

  5. 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.

  6. 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.

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

    International Nuclear Information System (INIS)

    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 p15INK4b 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 KrasG12D. In addition, we show that Dscr1 trisomy attenuates nuclear localization of nuclear factor of activated T-cells (NFAT) accompanied by upregulation of the p15Ink4b 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

  8. 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.

  9. Practice Bulletin No. 163 Summary: Screening for Fetal Aneuploidy.

    Science.gov (United States)

    2016-05-01

    Prenatal genetic screening is designed to assess whether a patient is at increased risk of having a fetus affected by a genetic disorder. In contrast, prenatal genetic diagnostic testing is intended to determine, with as much certainty as possible, whether a specific genetic disorder or condition is present in the fetus. The purpose of prenatal screening for aneuploidy is to provide an assessment of the woman's risk of carrying a fetus with one of the more common fetal aneuploidies. This is in contrast to prenatal diagnostic testing for genetic disorders, in which the fetal chromosomes are evaluated for the presence or absence of abnormalities in chromosome number, deletions, and duplications, or the fetal DNA is evaluated for specific genetic disorders. The wide variety of screening test options, each offering varying levels of information and accuracy, has resulted in the need for complex counseling by the health care provider and complex decision making by the patient. No one screening test is superior to other screening tests in all test characteristics. Each test has relative advantages and disadvantages. It is important that obstetrician-gynecologists and other obstetric care providers be prepared to discuss not only the risk of aneuploidy but also the benefits, risks, and limitations of available screening tests. Screening for aneuploidy should be an informed patient choice, with an underlying foundation of shared decision making that fits the patient's clinical circumstances, values, interests, and goals.The purpose of this Practice Bulletin is to provide current information regarding the available screening test options for fetal aneuploidy and to review their benefits, accuracy, and limitations. For information regarding prenatal diagnostic testing for genetic disorders, refer to Practice Bulletin No. 162, Prenatal Diagnostic Testing for Genetic Disorders. PMID:27101120

  10. Practice Bulletin No. 163: Screening for Fetal Aneuploidy.

    Science.gov (United States)

    2016-05-01

    Prenatal genetic screening is designed to assess whether a patient is at increased risk of having a fetus affected by a genetic disorder. In contrast, prenatal genetic diagnostic testing is intended to determine, with as much certainty as possible, whether a specific genetic disorder or condition is present in the fetus. The purpose of prenatal screening for aneuploidy is to provide an assessment of the woman's risk of carrying a fetus with one of the more common fetal aneuploidies. This is in contrast to prenatal diagnostic testing for genetic disorders, in which the fetal chromosomes are evaluated for the presence or absence of abnormalities in chromosome number, deletions, and duplications, or the fetal DNA is evaluated for specific genetic disorders. The wide variety of screening test options, each offering varying levels of information and accuracy, has resulted in the need for complex counseling by the health care provider and complex decision making by the patient. No one screening test is superior to other screening tests in all test characteristics. Each test has relative advantages and disadvantages. It is important that obstetrician-gynecologists and other obstetric care providers be prepared to discuss not only the risk of aneuploidy but also the benefits, risks, and limitations of available screening tests. Screening for aneuploidy should be an informed patient choice, with an underlying foundation of shared decision making that fits the patient's clinical circumstances, values, interests, and goals.The purpose of this Practice Bulletin is to provide current information regarding the available screening test options for fetal aneuploidy and to review their benefits, accuracy, and limitations. For information regarding prenatal diagnostic testing for genetic disorders, refer to Practice Bulletin No. 162, Prenatal Diagnostic Testing for Genetic Disorders. PMID:26938574

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

    International Nuclear Information System (INIS)

    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.

  12. 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.

  13. The CIN4 chromosomal instability qPCR classifier defines tumor aneuploidy and stratifies outcome in grade 2 breast cancer

    DEFF Research Database (Denmark)

    Szász, Attila Marcell; Li, Qiyuan; Eklund, Aron Charles;

    2013-01-01

    assessed the ability of CIN4 to stratify outcome in an independent cohort of patients diagnosed between 1999 and 2002. 185 formalin-fixed, paraffin-embedded (FFPE) samples were included in the qPCR measurement of CIN4 expression. In parallel, ploidy status of tumors was assessed by flow cytometry. We......PCR derived measure of tumor aneuploidy from FFPE tissue, stratifies grade 2 tumors into good and poor prognosis groups....

  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. Partial trisomy 16p in an adolescent with autistic disorder and Tourette`s syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Hebebrand, J.; Martin, M.; Remschmidt, H. [Philipps-Univ., Marburg (Germany)] [and others

    1994-09-15

    A partial trisomy 16p was identified in a 14-year-old male adolescent with autistic disorder. He additionally showed complex motor and vocal phenomena, including some simple tics which had first appeared in childhood. Whereas these simple tics were of subclinical significance, an additional diagnosis of Tourette`s syndrome (TS) appears justified. The case report illustrates the diagnostic difficulties in assessing psychiatric symptomatology associated with both disorders, especially complex motor and vocal phenomena. The cytogenetic finding is discussed critically in the light of other chromosome abnormalities reported in both TS and autistic disorder. Chromosome 16p should be considered as a candidate region especially for autistic disorder. 21 refs.

  16. 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.

  17. 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

  18. [The fertility of trisomy 21 sufferers. One case (author's transl)].

    Science.gov (United States)

    Grall, J Y; Le Goux, A M; Le Marec, B; Picard, F; Larget-Piet, L; Dubois, J

    A case of pregnancy in a patient with trisomy 21 with birth of a hypotrophic infant, with a normal caryotype but multiple malformations. This case illustrates the limitations on antenatal diagnosis by amniocentesis. Study of the literature confirms the unfavourable foetal prognosis as a result of the risk of transmission of the chromosomal abnormality and, secondly, the prevalence of incest. PMID:151263

  19. 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.

  20. ACMG statement on noninvasive prenatal screening for fetal aneuploidy.

    Science.gov (United States)

    Gregg, Anthony R; Gross, S J; Best, R G; Monaghan, K G; Bajaj, K; Skotko, B G; Thompson, B H; Watson, M S

    2013-05-01

    Noninvasive assessment of the fetal genome is now possible using next-generation sequencing technologies. The isolation of fetal DNA fragments from maternal circulation in sufficient quantity and sizes, together with proprietary bioinformatics tools, now allows patients the option of noninvasive fetal aneuploidy screening. However, obstetric care providers must become familiar with the advantages and disadvantages of the utilization of this approach as analysis of cell-free fetal DNA moves into clinical practice. Once informed, clinicians can provide efficient pretest and posttest counseling with the goal of avoiding patient harm. It is in the public's best interest that test results contain key elements and that laboratories adhere to established quality control and proficiency testing standards. The analysis of cell-free fetal DNA in maternal circulation for fetal aneuploidy screening is likely the first of major steps toward the eventual application of whole fetal genome/whole fetal exome sequencing. PMID:23558255

  1. 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.

  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. Frequency of aneuploidy related to age in porcine oocytes

    Czech Academy of Sciences Publication Activity Database

    Horňák, M.; Jeseta, M.; Musilová, P.; Pavlok, Antonín; Kubelka, Michal; Motlík, Jan; Rubeš, J.; Anger, Martin

    2011-01-01

    Roč. 6, č. 4 (2011), s. 1-5. E-ISSN 1932-6203 R&D Projects: GA ČR GA523/09/0743; GA AV ČR IAA501620801 Institutional research plan: CEZ:AV0Z50450515 Keywords : porcine * oocytes * aneuploidy Subject RIV: EE - Microbiology, Virology Impact factor: 4.092, year: 2011 http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0018892

  4. 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.

  5. 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

  6. 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.

  7. 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...

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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...

  15. Trisomy 21 Alters DNA Methylation in Parent-of-Origin-Dependent and -Independent Manners

    Science.gov (United States)

    Alves da Silva, Antônio Francisco; Machado, Filipe Brum; Pavarino, Érika Cristina; Biselli-Périco, Joice Matos; Zampieri, Bruna Lancia; da Silva Francisco Junior, Ronaldo; Mozer Rodrigues, Pedro Thyago; Terra Machado, Douglas; Santos-Rebouças, Cíntia Barros; Gomes Fernandes, Maria; Chuva de Sousa Lopes, Susana Marina; Lopes Rios, Álvaro Fabricio

    2016-01-01

    The supernumerary chromosome 21 in Down syndrome differentially affects the methylation statuses at CpG dinucleotide sites and creates genome-wide transcriptional dysregulation of parental alleles, ultimately causing diverse pathologies. At present, it is unknown whether those effects are dependent or independent of the parental origin of the nondisjoined chromosome 21. Linkage analysis is a standard method for the determination of the parental origin of this aneuploidy, although it is inadequate in cases with deficiency of samples from the progenitors. Here, we assessed the reliability of the epigenetic 5mCpG imprints resulting in the maternally (oocyte)-derived allele methylation at a differentially methylated region (DMR) of the candidate imprinted WRB gene for asserting the parental origin of chromosome 21. We developed a methylation-sensitive restriction enzyme-specific PCR assay, based on the WRB DMR, across single nucleotide polymorphisms (SNPs) to examine the methylation statuses in the parental alleles. In genomic DNA from blood cells of either disomic or trisomic subjects, the maternal alleles were consistently methylated, while the paternal alleles were unmethylated. However, the supernumerary chromosome 21 did alter the methylation patterns at the RUNX1 (chromosome 21) and TMEM131 (chromosome 2) CpG sites in a parent-of-origin-independent manner. To evaluate the 5mCpG imprints, we conducted a computational comparative epigenomic analysis of transcriptome RNA sequencing (RNA-Seq) and histone modification expression patterns. We found allele fractions consistent with the transcriptional biallelic expression of WRB and ten neighboring genes, despite the similarities in the confluence of both a 17-histone modification activation backbone module and a 5-histone modification repressive module between the WRB DMR and the DMRs of six imprinted genes. We concluded that the maternally inherited 5mCpG imprints at the WRB DMR are uncoupled from the parental allele

  16. 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 ...

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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

  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. Tetralogy of fallot in down syndrome (trisomy 21) - an uncommon association

    International Nuclear Information System (INIS)

    Down Syndrome (trisomy 21) is the common disorder among chromosomal anomalies. This is frequently associated with congenital a cyanotic heart disease. Tetralogy of fallot is an uncommon event in the trisomy 21. Tetralogy of fallot presents with cyanosis usually in the later part of infancy, but cyanosis is present since birth if Tetralogy of Fallot is accompanied with Down Syndrome. (author)

  5. 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.

  6. Cutaneous manifestations in trisomy 13 mosaicism: A rare case and review of the literature.

    Science.gov (United States)

    Wieser, Iris; Wohlmuth, Christoph; Rittinger, Olaf; Fischer, Thorsten; Wertaschnigg, Dagmar

    2015-10-01

    Trisomy 13 mosaicism is a rare genetic disorder affecting a small minority of all trisomy 13 cases. It occurs when two cell populations that are karyotypically different are present in the same individual and are derived from a single zygote. As a rule, the phenotype is mitigated to a less dysmorphic appearance and longer survival, making genetic counseling a difficult task. Capillary hemangiomas are a common feature of full trisomy 13, seen in 27-56% of all cases. We report on an 18-months-old girl with extensive cutaneous anomalies, mild dysmorphic features, and slight psychomotor delay, without structural defects and provide an up-to-date review of all cases of trisomy 13 mosaicism with skin involvement. To our knowledge, this is the second clinical report of a patient with trisomy 13 mosaicism with hemangiomas and port wine stains, but no structural defects. © 2015 Wiley Periodicals, Inc. PMID:25943247

  7. 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...

  8. Trisomy 3 mosaicism in a 5-year-old boy with multiple anomalies: A very rare case.

    Science.gov (United States)

    Yang, Yong-Jia; Yao, Xu; Guo, Jihong; Zhao, Liu; Tu, Ming; Qiou, Jun; Zhao, Rui; Luo, Yongqi; Zhu, Yi-Min

    2016-06-01

    Trisomy 3 mosaicism in live birth is exceedingly rare. In this study, we report a 5-year-old boy with trisomy 3 mosaicism who exhibits skeletal anomalies, atypical form of ectodermal dysplasias, refractory diarrhea, and normal intelligence. Fluorescence in situ hybridization and microsatellite marker analyses confirmed the existence of trisomy 3 mosaicism and suggested that the parental origin of the additional chromosome 3 in the trisomic cells was maternal. This report further delineated the trisomy 3 mosaicism in live births. The authors propose that both common phenotypes and phenotypic diversity exist on cases with trisomy 3 mosaicism. © 2016 Wiley Periodicals, Inc. PMID:27004455

  9. 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

    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 are...... highly correlated prognostic factors and that these two parameters identify the same subgroup of patients characterized by aparticularly favorable outcome....

  10. Non-invasive prenatal testing for aneuploidy and beyond

    DEFF Research Database (Denmark)

    Dondorp, Wybo; de Wert, Guido; Bombard, Yvonne;

    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 part of the screening offer. Depending on the health-care setting, different scenarios for NIPT-based screening....... 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...

  11. Data in brief: Transcriptome analysis of induced pluripotent stem cells from monozygotic twins discordant for trisomy 21

    Directory of Open Access Journals (Sweden)

    Youssef Hibaoui

    2014-12-01

    Full Text Available Down syndrome (DS, trisomy 21, is the most common viable chromosomal disorder, with an incidence of 1 in 800 live births. Its phenotypic characteristics include intellectual impairment and several other developmental abnormalities, for the majority of which the pathogenetic mechanisms remain unknown. In this “Data in Brief” paper, we sum up the whole genome analysis by mRNA sequencing of normal and DS induced pluripotent stem cells that was recently published by Hibaoui et al. in EMBO molecular medicine.

  12. 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.

  13. 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

  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. First Trimester Aneuploidy Screening Markers in Women with Pre-Gestational Diabetes Mellitus

    OpenAIRE

    Padmalatha Gurram; Peter Benn; James Grady; Anne-Marie Prabulos; Winston Campbell

    2014-01-01

    Objective: To investigate whether maternal serum pregnancy associated plasma protein-A (PAPP-A), total β human chorionic gonadotropin (hCG) levels and nuchal translucency (NT) measurements differ in women with pre-gestational diabetes mellitus (PGDM) compared to non-diabetic controls and to assess whether correction factors are needed for diabetic women in calculation of aneuploidy risks. Study Design: We performed a retrospective study of all women who underwent first trimester aneuploidy sc...

  16. 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.

  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. 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

  19. 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.

  20. Frequencies of aneuploidy and dominant lethal mutations in young female mice induced by low dose γ-rays

    International Nuclear Information System (INIS)

    Relationship between aneuploidy, dominant lethal mutations and doses in young feral mice induced by low dose γ-rays was examined. The results suggest that the frequencies of aneuploidy of embryos increased at 0.15 Gy, but increases at over 0.50 Gy after irradiation in groups. The frequencies of aneuploidy and dominant lethal mutations increased with increasing doses and fitted linear relationship. This dose-response relationship of trisomic was not significant. The frequency of dominant lethal mutations induced by 60Co γ irradiation is 5.59%. The effect of dominant lethal mutation is higher than that of the aneuploidy

  1. 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.

  2. 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

  3. 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...

  4. Ultrasonographic screening for trisomy 21 after 11 to 13+6 weeks of gestation

    International Nuclear Information System (INIS)

    Objective: To find a practical method for ultrasonographic screening for Trisomy 21 using nasal bone assement after 11 to 13+6 weeks of gestation. Methods: The risk of Trisomy 21 based on whether the nasal bone was present or absent and the length of nasal bone. Results: First trimester nasal bone length did not play a prominent role in ultrasonographic screening for trisomy 21 was predicted, but once the nasal bone was absent, it had a positive predictive value of 50%. There was no relationship between nasal bone and nucal translucency. Nucal translucency and other ultrasonographic markers must be taken into acount when the risk of Trisomy 21 was predicted. The length of nasal bone increased linearly with biparietal diameter in first the trimester. Conclusion: Presence or absence of the nasal bone should be noticed when doing ultrasonigraphic screening in the first trimester. Confident identification of an absent nasal bone has a high positive predictive value for trisomy 21 in the first trimester. Once a fetus is identified with an absent nasal bone, it shoud be provided with a cytological examination. NB and NT can be used as two independent ultrasononographic factors during screening for Trisomy 21. Nasal bone length increases linearly with biacrominal diameter in the first trimester. (authors)

  5. Hepatic failure, neonatal hemochromatosis and porto-pulmonary hypertension in a newborn with trisomy 21 - a case report

    OpenAIRE

    Poulik Janet; Bawle Erawati V; Joshi Aparna; Cortez Josef; Neil Erin; Zilberman Mark; El-Baba Mohammad F; Sood Beena G

    2010-01-01

    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); thi...

  6. Expression profiling reveals fundamental biological differences in acute myeloid leukemia with isolated trisomy 8 and normal cytogenetics

    OpenAIRE

    Virtaneva, Kimmo; Wright, Fred A; Tanner, Stephan M.; Yuan, Bo; William J. Lemon; Caligiuri, Michael A.; Bloomfield, Clara D.; de la Chapelle, Albert; Krahe, Ralf

    2001-01-01

    Acute myeloid leukemia (AML) is a heterogeneous group of diseases. Normal cytogenetics (CN) constitutes the single largest group, while trisomy 8 (+8) as a sole abnormality is the most frequent trisomy. How trisomy contributes to tumorigenesis is unknown. We used oligonucleotide-based DNA microarrays to study global gene expression in AML+8 patients with +8 as the sole chromosomal abnormality and AML-CN patients. CD34+ cells purified from normal bone marrow (BM) we...

  7. 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

  8. 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.

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

    International Nuclear Information System (INIS)

    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-κB), 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-κB) consecutive patients, aneuploidy was assessed by interphase fluorescent in situ hybridisation (FISH) for chromosome 1. NF-κB 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-κB 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 clinically useful in pre

  10. 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

  11. 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

  12. 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. PMID:24962971

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. First-trimester screening for trisomy 21 in Denmark

    DEFF Research Database (Denmark)

    Ekelund, C K; Petersen, O B; Skibsted, L;

    2011-01-01

    2007 (P < 0.0001). For women participating in first-trimester risk assessment in 2006 and 2007, the detection rate of T18 and T13 was 78.8% (95% CI, 71.0-86.7%). CONCLUSION: The number of T18 and T13 fetuses diagnosed before week 18 increased significantly after the introduction of a combined first......-trimester screening strategy for T21 in Denmark. In addition, the total number of fetuses diagnosed late in pregnancy and infants born with T18 or T13 decreased significantly. The national detection rate for T18 and T13 in the first trimester is comparable with detection rates found in modeled datasets and other......OBJECTIVES: 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...

  20. 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

  1. Molecular characterization of de novo secondary trisomy 13

    Energy Technology Data Exchange (ETDEWEB)

    Shaffer, L.G.; McCaskill, C.; Han, Jin-Yeong [Baylor College of Medicine, Houston, TX (United States); Choo, K.H.A. [Murdoch Institute, Melbourne (Australia); Cutillo, D.M.; Donnenfeld, A.E. [Pennyslvania Hospital, PA (United States); Weiss, L.; Van Dyke, D.L. [Henry Ford Hospital, Detroit, MI (United States)

    1994-11-01

    Unbalanced Robertsonian translocations are a significant cause of mental retardation and fetal wastage. The majority of homologous rearrangements of chromosome 21 in Down syndrome have been shown to be isochromosomes. Aside from chromosome 21, very little is known about other acrocentric homologous rearrangements. In this study, four cases of de novo secondary trisomy 13 are presented. FISH using alpha-satellite sequences, rDNA, and a pTRI-6 satellite I sequence specific to the short arm of chromosome 13 showed all four rearrangements to be dicentric an apparently devoid of ribosomal genes. Three of four rearrangements retained the pTRI-6 satellite I sequence. Case 1 was the exception, showing a deletion of this sequence in the rearrangement, although both parental chromosomes 13 had strong positive hybridization signals. Eleven microsatellite markers from chromosome 13 were also used to characterize the rearrangements. Of the four possible outcomes, one maternal Robertsonian translocation, two paternal isochromosomes, and one maternal isochromosomes were observed. A double recombination was observed in the maternally derived rob(13q13q). No recombination events were detected in any isochromosome. The parental origins and molecular chromosomal structure of these cases are compared with previous studies of de novo acrocentric rearrangements. 20 refs., 3 figs., 2 tabs.

  2. Racial variation in incidence of trisomy 21: survey of 57,742 Chinese deliveries.

    Science.gov (United States)

    Lau, T K; Fung, H Y; Rogers, M S; Cheung, K L

    1998-02-01

    The objective of this study was to establish whether the influence of advanced maternal age on the incidence of trisomy 21 in the local Chinese population is similar to that seen among European patients by comparing the observed number of trisomy 21 cases against the expected number which was calculated from age-specific Caucasian data and adjusted for intrauterine lethality and rate of amniocentesis. The obstetric and neonatal data of 57,742 pregnancies in ethnic Chinese were reviewed, of which 10.5% were from mothers age 35 or over. A total of 74 cases of trisomy 21 was detected (overall incidence of 1.28 per 1,000 deliveries). The expected number of trisomy 21 cases in mothers younger than 35 was 45.6, which was similar to the observed number of 43. Among mothers age 35 or above, the expected and observed numbers of cases were 38.52 and 31, respectively, again a difference not statistically significant. Therefore we conclude that there is no significant racial variation in the incidence of trisomy 21, both in the younger and older age groups, when comparing Chinese to Caucasian populations. PMID:9482644

  3. A female newborn having mosaicism with near-tetraploidy and trisomy 18.

    Science.gov (United States)

    Wada, Yuka; Kakiuchi, Satsuki; Mizuguchi, Koichi; Nakamura, Tomoo; Ito, Yushi; Sago, Haruhiko; Kosaki, Rika

    2016-05-01

    Tetraploidy is characterized by the presence of four complete sets of chromosomes in an individual. Full tetraploidy is usually considered lethal. To date, only ten live-births with the condition have been reported. Trisomy 18 without neonatal intensive treatment is also known to be fatal. We report a female newborn who had mosaicism with near-tetraploidy and trisomy 18 (94,XXXX,+18,+18/47,XX,+18). She had features of conditions. The most plausible mechanism of the formation was a failure of cytoplasmic cleavage at the first division of the zygote. The longer survival of the patient compared with the 10 previously reported live-births with non-mosaic tetraploidy may be due to the dominance of the trisomy cells. We suggest that non-tetraploid cells, even when trisomic for chromosome 18, might contribute to longer survival in comparison to non-mosaic tetrapolid patients. © 2016 Wiley Periodicals, Inc. PMID:26789424

  4. 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.

  5. 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.

  6. 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

  7. Causes and consequences of maternal age-related aneuploidy in oocytes: a review

    Czech Academy of Sciences Publication Activity Database

    Danylevska, Anna; Šebestová, Jaroslava

    2013-01-01

    Roč. 58, č. 2 (2013), s. 65-72. ISSN 0375-8427 R&D Projects: GA ČR GA523/09/0743; GA ČR GAP502/12/2201 Institutional support: RVO:67985904 Keywords : aneuploidy * oocyte * maternal age Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.756, year: 2013

  8. Revisiting tumour aneuploidy - the place of ploidy assessment in the molecular era.

    Science.gov (United States)

    Danielsen, Håvard E; Pradhan, Manohar; Novelli, Marco

    2016-05-01

    Chromosome instability (CIN) is gaining increasing interest as a central process in cancer. CIN, either past or present, is indicated whenever tumour cells harbour an abnormal quantity of DNA, termed 'aneuploidy'. At present, the most widely used approach to detecting aneuploidy is DNA cytometry - a well-known research assay that involves staining of DNA in the nuclei of cells from a tissue sample, followed by analysis using quantitative flow cytometry or microscopic imaging. Aneuploidy in cancer tissue has been implicated as a predictor of a poor prognosis. In this Review, we have explored this hypothesis by surveying the current landscape of peer-reviewed research in which DNA cytometry has been applied in studies with disease-appropriate clinical follow up. This area of research is broad, however, and we restricted our survey to results published since 2000 relating to seven common epithelial cancers (those of the breast; endometrium, ovary, and uterine cervix; oesophagus; colon and rectum; lung; prostate; and bladder). We placed particular emphasis on results from multivariate analyses to pinpoint situations in which the prognostic value of aneuploidy as a biomarker is strong compared with that of existing indicators, such as clinical stage, histological grade, and specific molecular markers. We summarize the implications of our findings for the prognostic use of ploidy analysis in the clinic and for the theoretical understanding of the role of CIN in carcinogenesis. PMID:26598944

  9. Identification of aneuploidy-inducing agents using cytokinesis-blocked human lymphocytes and an antikinetochore antibody

    Energy Technology Data Exchange (ETDEWEB)

    Eastmond, D.A.; Tucker, J.D.

    1989-01-01

    The identification of agents causing aneuploidy in humans, a condition associated with carcinogenesis and birth defects, is currently limited due to the highly skilled and time-consuming nature of cytogenetic analyses. We report the development of a new simple and rapid assay to identify aneuploidy-inducing agents (aneuploidogens). The assay involves the chemical- or radiation-induced formation of micronuclei in cytokinesis-blocked human lymphocytes and the use of an antikinetochore antibody to determine whether the micronuclei contain centromeres--a condition indicating a high potential for aneuploidy. All agents tested produced dose-related increases in the frequency of micronucleated cells. The micronucleated cells induced by the known aneuploidogens--colchicine, vincristine sulfate, and diethylstilbestrol--contained kinetochore-positive micronuclei 92, 87, and 76% of the time, respectively. In contrast, the micronucleated cells induced by the potent clastogens--ionizing radiation and sodium arsenite--contained kinetochore-positive micronuclei only 3 and 19% of the time, respectively. These results indicate that this relatively simple assay can discriminate between aneuploidogens and clastogens and may allow a more rapid identification of environmental and therapeutic agents with aneuploidy-inducing potential.

  10. 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…

  11. 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

  12. 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

  13. 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

  14. Modification of radio-sensitivity of human normal and trisomy-21 fibroblasts by irradiation under hypoxic condition

    International Nuclear Information System (INIS)

    The authors previously reported that fibroblasts from Trisomy-21 patients were moderately radiosensitive; however, DMSO reduced x-ray induced cytotoxicity in trisomy-21 cells more than in normal fibroblasts. Human trisomy-21 cells contain 150% the normal level of Cu-Zn SOD (superoxide dismutase). These genes are located on chromosome-21. Production of superoxide radical anions (O/sub 2//sup -/) is an initial radiation-induced reaction, followed by H/sub 2/O/sub 2/, OH . and finally H/sub 2/O. In present study, confluent cultures of skin fibroblasts form normal and trisomy-21 individuals were irradiated in air and under hypoxic conditions. The cells were subcultured immediately and reseeded at low density to measure colony forming ability. The D/sub O/ of the survival curves for trisomy-21 cell strains irradiated in air were 80-100 rads with no or small shoulder regions, as compared with 120-150 rads with noticeable shoulder regions for normal strains. The enhancement ratios for survival of trisomy-21 fibroblasts irradiated under hypoxic conditions were nearly 2-3 times higher than for normal fibroblasts. The enhanced survival under hypoxic conditions was due to large increases in the shoulder regions and some increase in D/sub O/ values for both normal and Trisomy-21 cells. Further experiments are currently in progress to better define this effect

  15. 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.

  16. 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

  17. 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...

  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. Left ventricle shortening fraction: a comparison between euploid and trisomy 21 fetuses in the first trimester

    Czech Academy of Sciences Publication Activity Database

    Calda, P.; Břešťák, M.; Tomek, V.; Ošťádal, Bohuslav; Sonek, J.

    2010-01-01

    Roč. 30, č. 4 (2010), s. 368-371. ISSN 0197-3851 R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : trisomy 21 * first trimester * shortening fraction of the left ventricle Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 2.152, year: 2010

  20. 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...

  1. 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

  2. Bilateral neck cysts as an isolated sonographic finding in the antenatal detection of fetal aneuploidy: a case report

    OpenAIRE

    Abi-Nader, Khalil; Filippi, Elisa; Pandya, Pranav P; Peregrine, Elisabeth

    2009-01-01

    Isolated fetal lateral neck cysts can represent a cystic hygroma or a developmental remnant cyst. In the absence of an increased nuchal translucency or associated malformations the risk of aneuploidy has been considered negligible. Still, dysmorphology in aneuploid fetuses might not be evident except at a later stage. We report on a case of isolated fetal bilateral neck cysts where aneuploidy was suspected and confirmed despite the lack of associated morphologic abnormalities.

  3. 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...

  4. 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...

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

    Directory of Open Access Journals (Sweden)

    Elham SEYYED-KAVOOSI

    2015-10-01

    Full Text Available 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-vided 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.

  6. [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

  7. 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

  8. 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

  9. 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.

  10. 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...

  11. 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...

  12. 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...

  13. 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...

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

    Science.gov (United States)

    Barranger, Audrey; Benabdelmouna, Abdellah; Dégremont, Lionel; Burgeot, Thierry; Akcha, Farida

    2015-02-01

    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. PMID:25498420

  15. PGD and aneuploidy screening for 24 chromosomes: advantages and disadvantages of competing platforms.

    Science.gov (United States)

    Bisignano, A; Wells, D; Harton, G; Munné, S

    2011-12-01

    Diagnosis of embryos for chromosome abnormalities, i.e. aneuploidy screening, has been invigorated by the introduction of microarray-based testing methods allowing analysis of 24 chromosomes in one test. Recent data have been suggestive of increased implantation and pregnancy rates following microarray testing. Preimplantation genetic diagnosis for infertility aims to test for gross chromosome changes with the hope that identification and transfer of normal embryos will improve IVF outcomes. Testing by some methods, specifically single-nucleotide polymorphism (SNP) microarrays, allow for more information and potential insight into parental origin of aneuploidy and uniparental disomy. The usefulness and validity of reporting this information is flawed. Numerous papers have shown that the majority of meiotic errors occur in the egg, while mitotic errors in the embryo affect parental chromosomes at random. Potential mistakes made in assigning an error as meiotic or mitotic may lead to erroneous reporting of results with medical consequences. This study's data suggest that the bioinformatic cleaning used to 'fix' the miscalls that plague single-cell whole-genome amplification provides little improvement in the quality of useful data. Based on the information available, SNP-based aneuploidy screening suffers from a number of serious issues that must be resolved. PMID:21856229

  16. Nuclear pore protein NUP88 activates anaphase-promoting complex to promote aneuploidy.

    Science.gov (United States)

    Naylor, Ryan M; Jeganathan, Karthik B; Cao, Xiuqi; van Deursen, Jan M

    2016-02-01

    The nuclear pore complex protein NUP88 is frequently elevated in aggressive human cancers and correlates with reduced patient survival; however, it is unclear whether and how NUP88 overexpression drives tumorigenesis. Here, we show that mice overexpressing NUP88 are cancer prone and form intestinal tumors. To determine whether overexpression of NUP88 drives tumorigenesis, we engineered transgenic mice with doxycycline-inducible expression of Nup88. Surprisingly, NUP88 overexpression did not alter global nuclear transport, but was a potent inducer of aneuploidy and chromosomal instability. We determined that NUP88 and the nuclear transport factors NUP98 and RAE1 comprise a regulatory network that inhibits premitotic activity of the anaphase-promoting complex/cyclosome (APC/C). When overexpressed, NUP88 sequesters NUP98-RAE1 away from APC/CCDH1, triggering proteolysis of polo-like kinase 1 (PLK1), a tumor suppressor and multitasking mitotic kinase. Premitotic destruction of PLK1 disrupts centrosome separation, causing mitotic spindle asymmetry, merotelic microtubule-kinetochore attachments, lagging chromosomes, and aneuploidy. These effects were replicated by PLK1 insufficiency, indicating that PLK1 is responsible for the mitotic defects associated with NUP88 overexpression. These findings demonstrate that the NUP88-NUP98-RAE1-APC/CCDH1 axis contributes to aneuploidy and suggest that it may be deregulated in the initiating stages of a broad spectrum of human cancers. PMID:26731471

  17. 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

  18. 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

  19. First Trimester Aneuploidy Screening Markers in Women with Pre-Gestational Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Padmalatha Gurram

    2014-05-01

    Full Text Available Objective: To investigate whether maternal serum pregnancy associated plasma protein-A (PAPP-A, total β human chorionic gonadotropin (hCG levels and nuchal translucency (NT measurements differ in women with pre-gestational diabetes mellitus (PGDM compared to non-diabetic controls and to assess whether correction factors are needed for diabetic women in calculation of aneuploidy risks. Study Design: We performed a retrospective study of all women who underwent first trimester aneuploidy screening (11 + 0 to 13 + 6 weeks from 2005 to 2011. The primary study outcome was the difference in PAPP-A, β-hCG and NT multiples of median between women with PGDM and non-diabetic women. Results: Of 6741 eligible patients, 103 patients with PGDM were using insulin and 4 patients were using oral hypoglycemic agents; the latter were excluded due to small number. There was 12% reduction of median PAPP-A (p = 0.001 and 18% reduction of median hCG (p = 0.006 in women with PGDM receiving insulin. There was no difference in NT. Conclusions: In women with PGDM receiving insulin, PAPP-A and β-hCG levels are significantly lower compared to non-diabetic women. This suggests that when calculating risks for aneuploidy, correction factors should be considered to adjust PAPP-A and β-hCG concentrations to those seen in non-diabetic women.

  20. 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.

  1. 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.

    Science.gov (United States)

    Paulsson, Kajsa; Forestier, Erik; Andersen, Mette K; Autio, Kirsi; Barbany, Gisela; Borgström, Georg; Cavelier, Lucia; Golovleva, Irina; Heim, Sverre; Heinonen, Kristiina; Hovland, Randi; Johannsson, Johann H; Kjeldsen, Eigil; Nordgren, Ann; Palmqvist, Lars; Johansson, Bertil

    2013-09-01

    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(11q23), 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 are highly correlated prognostic factors and that these two parameters identify the same subgroup of patients characterized by a particularly favorable outcome. PMID:23645689

  2. Segmental trisomy of mouse chromosome 17: introducing an alternative model of Down syndrome

    Czech Academy of Sciences Publication Activity Database

    Forejt, Jiří; Vacík, Tomáš; Gregorová, Soňa

    2003-01-01

    Roč. 4, - (2003), s. 647-652. ISSN 1531-6912 R&D Projects: GA MŠk LN00A079; GA ČR GV204/98/K015 Grant ostatní: HHMI(US) 555000306 Institutional research plan: CEZ:AV0Z5052915 Keywords : segmental aneuploidy * Down´s syndrome * gene dosage Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.297, year: 2003

  3. 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...... anomalies. Unlike the partial trisomy 9q34-qter, partial monosomy 8q24.3-qter has no distinct phenotype. Here we report a four years old female patient with partial trisomy 9q34-qter and partial monosomy 8q24.3-qter due to the maternal translocation t(8;9)(q24.3;q34. I). She has developmental delay...

  4. Normal psychomotor development in a child with mosaic trisomy and pericentric inversion of chromosome 9.

    OpenAIRE

    Frydman, M; Shabtal, F; Halbrecht, I; Elian, E

    1981-01-01

    A female infant with trisomy 9 in 58% of her cells is reported. Multiple congenital malformations were present, but she had normal psychomotor development. A pericentric inversion involving a portion of the centromeric heterochromatin of chromosome 9 was identified in the patient and her mother. This variant chromosome 9 was present in duplicate in the trisomic line. Since similar variants of 9qh have been found repeatedly in this syndrome, we feel that this association may be a non-random one.

  5. Neurocognitive functioning of a child with partial trisomy 6 and monosomy 21

    OpenAIRE

    Katzenstein, Jennifer M.; OGHALAI, JOHN S; TONINI, ROSS; Baker, Dian; Haymond, Jody; Caudle, Susan E.

    2009-01-01

    This case study describes the neurocognitive presentation of a child with identified genetic abnormalities of trisomy 6 and monosomy 21 who was evaluated as part of a standard medical protocol for cochlear implantation following diagnosis of profound sensorineural hearing loss. This child received neurocognitive testing prior to cochlear implantation and approximately 12 months post-activation of his cochlear implant. While he has not fully developed oral language, his presentation suggested ...

  6. 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...

  7. Partial and complete trisomy 14 mosaicism: clinical follow-up, cytogenetic and molecular analysis

    OpenAIRE

    Salas-Labadía, Consuelo; Lieberman, Esther; Cruz-Alcívar, Roberto; Navarrete-Meneses, Pilar; Gómez, Samuel; Cantú-Reyna, Consuelo; Buiting, Karin; Durán-McKinster, Carola; Pérez-Vera, Patricia

    2014-01-01

    Background Trisomy 14 mosaicism is a rare chromosomal abnormality. It is associated with multiple congenital anomalies. We report a 15 year-old female with an unusual karyotype with three cell lines: 47,XX,+mar/47,XX,+14/46,XX. At six months old she had short stature, cleft palate, hyperpigmented linear spots in arms and legs and developmental delay. At present, she has mild facial dysmorphism and moderate mental retardation. Methods Cytogenetic analysis was performed in peripheral blood lymp...

  8. Trisomy-X with estrous cycle anomalies in two female dogs

    OpenAIRE

    O'Connor, CL; Schweizer, C; Gradil, C; Schlafer, D; Lopate, C.; Prociuk, U; Meyers-Wallen, VN; Casal, ML

    2011-01-01

    Two female dogs were presented with a history of abnormal estrous cycles and infertility, despite multiple breedings. Medical therapy to correct the cycle anomalies did not result in pregnancy. Cytogenetic analysis of blood lymphocyte cultures in each dog revealed three copies of the X chromosome in each cell, constituting a 79,XXX karyotype (trisomy-X). Both dogs were eventually ovariohysterectomised and histological evaluation revealed hypoplastic ovaries and an absence of normal follicular...

  9. 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.

  10. Repair of x-ray induced chromosomal damage in trisomy 2- and normal diploid lymphocytes

    International Nuclear Information System (INIS)

    The frequency of chromosomal aberrations produced by x-rays is greater in lymphocytes cultured from trisomy 21 patients (Down's syndrome) than from normal diploid donors. This increase, which can be detected by a micronucleus assay for chromosomal damage, was postulated by us to result from a defect in the rejoining system which repairs chromosomal breaks. The postulated defect would result in a longer rejoining time, therapy permitting more movement of broken ends and thus enhancing the frequency of exchanges. To test this possibility, the time required for the rejoining (repair) of chromosome breaks was measured in lymphocytes from five Down's syndrome (four trisomy 21 and one D/G translocation partial trisomy 21) donors, from a monosomy 21 donor, and from five diploid donors. The rejoining time was reduced in the Down's syndrome lymphocytes in comparison to the normal diploid and monosomy 21 lymphocytes. Thus the repair of chromosome breaks, far from being defective as evidenced by a longer rejoining time in Down's syndrome cells, occurred more rapidly than in normal cells

  11. [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

  12. 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. PMID:26200104

  13. 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.

  14. 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....

  15. 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

  16. 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; Luppa, P; Ortiz, J.U.; Ferri, M; Sancken, U; Vereecken, Annie; Wiedemann, U; Zitzler, Jürgen; Nicolaides, K.H.

    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...

  17. Early Biochemical Screening for Fetal Aneuploidy in the First Trimester

    DEFF Research Database (Denmark)

    Tørring, Niels

    2013-01-01

    assays showed slopes of 0.94 and 0.95 and Pearson’s correlation of r = 0.981 and r = 0.987 respectively. Similar comparison to AutoDELFIA PerkinElmer Perkin gave slopes of 0,83 (free βhCG) and 1.20 (PAPP-A). With a cut off at 1:300 the overall sensitivity of the first trimester screening including nuchal...

  18. 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.

  19. 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

  20. 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

  1. 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。

  2. 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。

  3. Failure to thrive as primary feature in two patients with subtle chromosomal aneuploidy: Interstitial deletion 2q33

    Energy Technology Data Exchange (ETDEWEB)

    Grace, K.; Mulla, W.; Stump, T. [Children`s Hospital of Philadelpha, PA (United States)] [and others

    1994-09-01

    It is well known that patients with chromosomal aneuploidy present with multiple congenital anomalies and dysmorphia, and that they may have associated failure to thrive. However, rarely is failure to thrive the predominant presenting feature. We report two such patients. Patient 1 had a marked history of failure to thrive, (weight 50% for 5 1/2 months at 20 months, length 50% for 15 months at 20 months). Patient 2 was noted to be growth retarded at 2 months upon presenting to the hospital with respiratory symptoms (weight 50% for a newborn, length 50% for 36 weeks gestation). There was relative head sparing in both patients. Chromosome analysis in patient 1, prompted by a negative work-up for the failure to thrive, and emerging evidence of developmental delay, revealed a 46,XY,del(2)(q32.2q33) karyotype. Chromosome analysis in patient 2, done as part of a complete workup for the failure to thrive, revealed a 46,XX,del(2)(q33.2q33.2 or q33.2q33.3) karyotype. On careful examination, subtle dysmorphic features were seen. In both patients these included a long flat philtrum, thin upper lip and high arched palate. Patient 1 also had a small posterior cleft of the palate. These patients have the smallest interstitial deletions of chromosome 2 so far reported. Their deletions overlap within 2q33 although they are not identical. Review of the literature reveals 15 patients with interstitial deletions which include 2q33. Marked growth retardation is reported in 14 of these cases. Cleft palate/abnormal uvula were frequently associated. These cases illustrate the need to include high resolution chromosomal studies as part of a complete work-up for unexplained failure to thrive.

  4. 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.

  5. 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.

  6. 1,2-propanediol-induced premature centromere separation in mouse oocytes and aneuploidy in one-cell zygotes.

    Science.gov (United States)

    Mailhes, J B; Young, D; London, S N

    1997-07-01

    Aneuploidy in germ cells results in reproductive failure and mental and physical disorders in humans. Unfortunately, little is known about the causes and mechanisms of aneuploidy induction. The objective of this study was to test the hypothesis that propylene glycol (1,2-propanediol; PG) induces cytogenetic aberrations in mouse metaphase II (MII) oocytes that predispose zygotes to aneuploidy. Female ICR mice received 7.5 IU eCG and 5.0 IU hCG 48 h later. PG doses of 1300, 2600, and 5200 mg/kg body weight were given 3 h post-hCG; controls received the solvent deionized water. Ovulated oocytes were collected 16 h after administration of PG and processed for cytogenetic analysis. For the one-cell zygote cytogenetic study, females were given PG and paired (1:1) with ICR males for 16 h. Females that mated were given 2 x 10(-3) M colchicine 22 h post-PG, and zygotes were collected 18 h later. PG significantly (p separation (PCS) and the proportion of aneuploid one-cell zygotes. These results support the hypothesis that PG-induced PCS in MII oocytes predisposes zygotes to aneuploidy. PMID:9209085

  7. 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

  8. Neurocognitive functioning of a child with partial trisomy 6 and monosomy 21.

    Science.gov (United States)

    Katzenstein, Jennifer M; Oghalai, John S; Tonini, Ross; Baker, Dian; Haymond, Jody; Caudle, Susan E

    2009-01-01

    This case study describes the neurocognitive presentation of a child with identified genetic abnormalities of trisomy 6 and monosomy 21 who was evaluated as part of a standard medical protocol for cochlear implantation following diagnosis of profound sensorineural hearing loss. This child received neurocognitive testing prior to cochlear implantation and approximately 12 months post-activation of his cochlear implant. While he has not fully developed oral language, his presentation suggested improvement in overall skills since the activation of the cochlear implant; however, less than would be expected for a typically developing child. PMID:19172430

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. When does maternal age-dependent trisomy 21 arise relative to meiosis?

    Energy Technology Data Exchange (ETDEWEB)

    Chang-Jiang Zheng [National Inst. of Deafness and Other Communication Disorders, Bethesda, MD (United States); Byers, B. [Univ. of Washington, Seattle, WA (United States)

    1996-07-01

    Polymorphic DNA markers have recently been used to estimate the fraction of trisomy 21 (Down syndrome) cases that may be attributable to postzygotic nondisjunction - indicative of a loss in the fidelity of the first few cell divisions after fertilization. In these studies, a postzygotic nondisjunction is defined as a case in which two chromosomes of the trisomic set are homozygous for all informative markers (i.e., for those markers that were heterozygous in their parent of origin). These studies estimate that the postzygotic mutation mechanism accounts for 4.5% (11/238) and 3.5% (9/255) of their cases, respectively, but their estimates may actually be conservative, since all noninformative haplotypes (frequency not reported) are arbitrarily attributed to meiosis II-type nondisjunction. Nevertheless, even the conservative estimates would, if confirmed, constitute a new and nonnegligible source of chromosomal segregation errors leading to trisomy. These studies` conclusions are supported by the observation that the 20 reported {open_quotes}postzygotic{close_quotes} cases (5 paternal and 15 maternal) appear to be less dependent on maternal age (mean maternal age 28.4 years) than maternal meiosis I-type failures (mean maternal age 31.2 years). However, given the limited sample size involved, one should be cautious in positing the absence of a maternal age effect. 5 refs., 1 fig.

  15. 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.

  16. Proliferative kinetics and chromosome damage in trisomy 21 lymphocyte cultures exposed to gamma-rays and bleomycin

    International Nuclear Information System (INIS)

    Lymphocytes from patients with Down's syndrome (trisomy 21) have been investigated for cell cycle kinetics, cell proliferation delays, and chromosomal aberrations after exposure to gamma-rays or bleomycin. Analysis by sister chromatid differential staining revealed that trisomy 21 lymphocytes started cell cycling about 5 hr earlier than did normal diploid lymphocytes after phytohemagglutinin stimulation as a whole, but that cycling trisomic and normal cells had the same mean cell cycle times. When exposed to gamma-rays or bleomycin in G0, trisomy 21 lymphocytes showed a 30% or, on average, 50% longer duration of cell turnover times, respectively, than normal cells; only bleomycin-treated trisomic cells had a biphasic dose-response. Frequencies of dicentrics and rings in first-division cells after gamma-ray or bleomycin exposure were twice as high in trisomic cells as in normal cells. The frequency of aberrations decreased by 50% (gamma-ray-exposed) or 65 to 85% (bleomycin-treated) through successive divisions; trisomic cells showed a more marked decline in aberration yields compared to normal cells after bleomycin treatment. These data support the idea that circulating lymphocytes in trisomy 21 patients have a shorter average life span or a younger average age

  17. 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.

  18. 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…

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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; Kirkegaard, Ida; Nørgaard, Pernille; Sørensen, Steen; Jørgensen, Finn Stener; Friis-Hansen, Lennart; Uldbjerg, Niels; Tørring, Niels; Petersen, Olav Bjørn; Tabor, Ann

    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...

  4. 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.

  5. 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...

  6. 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

  7. Sex chromosome trisomies in Europe: prevalence, prenatal detection and outcome of pregnancy

    DEFF Research Database (Denmark)

    Boyd, Patricia Anne; Loane, Maria; Garne, Ester; Khoshnood, Babak; Dolk, Helen

    2011-01-01

    to 1 year of age represents 12% of the prevalence expected from cytogenetic studies of newborn babies, as the majority of cases are never diagnosed or are diagnosed later in life. There is a wide variation between European countries in prevalence, prenatal detection and TOPFA proportions, related to......This study aims to assess prevalence and pregnancy outcome for sex chromosome trisomies (SCTs) diagnosed prenatally or in the first year of life. Data held by the European Surveillance of Congenital Anomalies (EUROCAT) database on SCT cases delivered 2000-2005 from 19 population-based registries in...... differences in screening policies as well as organizational and cultural factors.European Journal of Human Genetics advance online publication, 25 August 2010; doi:10.1038/ejhg.2010.148....

  8. [Classic maternal phenylketonuria and sonographic evidence of fetal trisomy 21: first description].

    Science.gov (United States)

    Lehnen, H; Vinke, M; Schwennicke, C; Pascheberg, U

    2009-02-01

    Phenylketonuria is the best known pathology of amino acid metabolism. Presented here is the case of a 23-year-old prima gravida with phenylketonuria since birth. After delivery, her child was diagnosed with free trisomy 21. Abnormal sonographic signs such as bilateral hydrothorax, polyhydramnion, and short femura under the 10th percentile could be demonstrated in the ultrasound scan at 33 weeks of gestation. Regularly measured maternal phenylalanine levels during the complete pregnancy as well as preconceptionally were always under the embryopathic cutoff point of 1 200 micromoles/L (20 mg/L). An association seems unlikely. This is the first description of such a constellation according to a literature search (PubMed, Cochrane Library). PMID:19259898

  9. Frequency of Prenatal Cytogenetic Diagnosis and Pregnancy Outcomes by Maternal Race–Ethnicity, and the Effect on the Prevalence of Trisomy 21, Metropolitan Atlanta, 1996–2005

    OpenAIRE

    Jackson, Jodi M.; Crider, Krista S.; Cragan, Janet D.; Rasmussen, Sonja A.; Olney, Richard S.

    2013-01-01

    The prevalence of trisomy 21 has been reported to differ by race–ethnicity, however, the results are inconsistent and the cause of the differences is unknown. Using data from 1996 to 2005 from the Metropolitan Atlanta Congenital Defects Program (MACDP), we analyzed the use of prenatal cytogenetic testing and the subsequent use of elective termination among pregnancies affected with any MACDP-eligible birth defect and trisomy 21, by maternal race–ethnicity. We then examined whether these facto...

  10. 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...

  11. 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.

  12. 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.

  13. 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

  14. Cytokinesis failure and successful multipolar mitoses drive aneuploidy in glioblastoma cells.

    Science.gov (United States)

    Telentschak, Sergej; Soliwoda, Mark; Nohroudi, Klaus; Addicks, Klaus; Klinz, Franz-Josef

    2015-04-01

    Glioblastoma (GB) is the most frequent human brain tumor and is associated with a poor prognosis. Multipolar mitosis and spindles have occasionally been observed in cultured glioblastoma cells and in glioblastoma tissues, but their mode of origin and relevance have remained unclear. In the present study, we investigated a novel GB cell line (SGB4) exhibiting mitotic aberrations and established a functional link between cytokinesis failure, centrosome amplification, multipolar mitosis and aneuploidy in glioblastoma. Long-term live cell imaging showed that >3% of mitotic SGB4 cells underwent multipolar mitosis (tripolar>tetrapolar>pentapolar). A significant amount of daugther cells generated by multipolar mitosis were viable and completed several rounds of mitosis. Pedigree analysis of mitotic events revealed that in many cases a bipolar mitosis with failed cytokinesis occurred prior to a multipolar mitosis. Additionally, we observed that SGB4 cells were also able to undergo a bipolar mitosis after failed cytokinesis. Colchicine-induced mitotic arrest and metaphase spreads demonstrated that SGB4 cells had a modal chromosome number of 58 ranging from 23 to 170. Approximately 82% of SGB4 cells were hyperdiploid (47-57 chromosomes) or hypotriploid (58-68 chromosomes). In conclusion, SGB4 cells passed through multipolar cell divisions and generated viable progeny by reductive mitoses. Our results identified cytokinesis failure occurring before and after multipolar or bipolar mitoses as important mechanisms to generate chromosomal heterogeneity in glioblastoma cells. PMID:25625503

  15. 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

  16. 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

  17. Intelligence and achievement in children with extra X aneuploidy: A longitudinal perspective

    Energy Technology Data Exchange (ETDEWEB)

    Rovet, J.; Bailey, J. [Hospital for Sick Children, Toronto (Canada); Netley, C. [Lakehead Univ., Ontario (Canada)] [and others

    1995-10-09

    Forty-seven children (35 male, 12 female) identified as having a supernumerary X chromosome by neonatal screening were studied psychologically from childhood to late adolescence. This paper compares their findings relative to sibling controls on tests of intelligence and achievement collected over a 14-year period. Children with a supernumerary X chromosome were found to score consistently below controls on Verbal IQ and subtests comprising the Verbal Comprehension factor but they did not differ on Performance IQ, which was in the normal range. At all ages, they showed poorer reading and arithmetic achievement; relative risk for reading and arithmetic impairment was 2.6 and 2.6 in males and 1.1 and 1.7 in females. Males with an extra X chromosome were more likely to receive special education than females, who more often failed a grade. Academic achievement was not affected in aneuploid children with higher levels of intelligence. Overall, these results suggest milder impairment than previously reported, particularly among trisomy X females. 49 refs., 5 tabs.

  18. 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

  19. 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

  20. 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.

  1. Chronic up-regulation of the SHH pathway normalizes some developmental effects of trisomy in Ts65Dn mice

    OpenAIRE

    Dutka, Tara; Hallberg, Dorothy; Reeves, Roger H.

    2014-01-01

    Down Syndrome (DS) is a highly complex developmental genetic disorder caused by trisomy for human chromosome 21 (Hsa21). All individuals with DS exhibit some degree of brain structural changes and cognitive impairment; mouse models such as Ts65Dn have been instrumental in understanding the underlying mechanisms. Several phenotypes of DS might arise from a reduced response of trisomic cells to the Sonic Hedgehog (SHH) growth factor. If all trisomic cells show a similar reduced response to SHH,...

  2. 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...

  3. 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...

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. MATERNAL AGE EFFECT: THE ENIGMA OF DOWN SYNDROME AND OTHER TRISOMIC CONDITIONS

    Science.gov (United States)

    Aneuploidy is the most frequently observed chromosome abnormality in human liveborn, abortuses, and oocytes. he only etiological factor that has been established is advanced maternal age for the occurrence of trisomies, particularly trisomy 21 which causes Down syndrome. he mater...

  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. Simultaneous suppression of epidermal growth factor receptor and c-erbB-2 reverses aneuploidy and malignant phenotype of a human ovarian carcinoma cell line.

    Science.gov (United States)

    Pack, Svetlana D; Alper, Ozgül M; Stromberg, Kurt; Augustus, Meena; Ozdemirli, Metin; Miermont, Anne M; Klus, Greg; Rusin, Marek; Slack, Rebecca; Hacker, Neville F; Ried, Thomas; Szallasi, Zoltan; Alper, Ozge

    2004-02-01

    Coexpression of epidermal growth factor receptor (EGFR) and c-erbB-2 in 47-68% of ovarian cancer cells indicate their strong association with tumor formation. We examined the effects of simultaneous antisense- or immunosuppression of EGFR and c-erbB-2 expression on the invasive phenotype, aneuploidy, and genotype of cultured human ovarian carcinoma cells (NIH:OVCAR-8). We report here that suppression of both EGFR and c-erbB-2 results in regression of aneuploidy and genomic imbalances in NIH:OVCAR-8 cells, restores a more normal phenotype, and results in a more normal gene expression profile. Combined with cytogenetic analysis, our data demonstrate that the regression of aneuploidy is due to the selective apoptosis of double antisense transfected cells with highly abnormal karyotype. PMID:14871800

  12. Mutual information analysis as a tool to assess the role of aneuploidy in the generation of cancer-associated differential gene expression patterns.

    Science.gov (United States)

    Klus, G T; Song, A; Schick, A; Wahde, M; Szallasi, Z

    2001-01-01

    Most human tumors are characterized by: (1) an aberrant set of chromosomes, a state termed aneuploidy; (2) an aberrant gene expression pattern; and (3) an aberrant phenotype of uncontrolled growth. One of the goals of cancer research is to establish causative relationships between these three important characteristics. In this paper we were searching for evidence that aneuploidy is a major cause of differential gene expression. We describe how mutual information analysis of cancer-associated gene expression patterns could be exploited to answer this question. In addition to providing general guidelines, we have applied the proposed analysis to a recently published breast cancer-associated gene expression matrix. The results derived from this particular data set provided preliminary evidence that mutual information analysis may become a useful tool to investigate the link between differential gene expression and aneuploidy. PMID:11262960

  13. 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

  14. 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.

  15. 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. PMID:25146308

  16. Triangulating the sexually dimorphic brain through high-resolution neuroimaging of murine sex chromosome aneuploidies

    Science.gov (United States)

    Lue, YanHe; Probst, Frank; Greenstein, Deanna; Giedd, Jay; Wang, Christina; Lerch, Jason; Swerdloff, Ronald

    2016-01-01

    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 colocalized 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. PMID:25146308

  17. 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

  18. 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.

  19. Perturbations of heart development and function in cardiomyocytes from human embryonic stem cells with trisomy 21.

    Science.gov (United States)

    Bosman, Alexis; Letourneau, Audrey; Sartiani, Laura; Del Lungo, Martina; Ronzoni, Flavio; Kuziakiv, Rostyslav; Tohonen, Virpi; Zucchelli, Marco; Santoni, Federico; Guipponi, Michel; Dumevska, Biljana; Hovatta, Outi; Antonarakis, Stylianos E; Jaconi, Marisa E

    2015-05-01

    Congenital heart defects (CHD) occur in approximately 50% of patients with Down syndrome (DS); the mechanisms for this occurrence however remain unknown. In order to understand how these defects evolve in early development in DS, we focused on the earliest stages of cardiogenesis to ascertain perturbations in development leading to CHD. Using a trisomy 21 (T21) sibling human embryonic stem cell (hESC) model of DS, we show that T21-hESC display many significant differences in expression of genes and cell populations associated with mesodermal, and more notably, secondary heart field (SHF) development, in particular a reduced number of ISL1(+) progenitor cells. Furthermore, we provide evidence for two candidate genes located on chromosome 21, ETS2 and ERG, whose overexpression during cardiac commitment likely account for the disruption of SHF development, as revealed by downregulation or overexpression experiments. Additionally, we uncover an abnormal electrophysiological phenotype in functional T21 cardiomyocytes, a result further supported by mRNA expression data acquired using RNA-Seq. These data, in combination, revealed a cardiomyocyte-specific phenotype in T21 cardiomyocytes, likely due to the overexpression of genes such as RYR2, NCX, and L-type Ca(2+) channel. These results contribute to the understanding of the mechanisms involved in the development of CHD. Stem Cells 2015;33:1434-1446. PMID:25645121

  20. De novo 7p partial trisomy characterized by subtelomeric FISH and whole-genome array in a girl with mental retardation

    Directory of Open Access Journals (Sweden)

    N Chandra

    2011-10-01

    Full Text Available Abstract Chromosome rearrangements involving telomeres have been established as one of the major causes of idiopathic mental retardation/developmental delay. This case of 7p partial trisomy syndrome in a 3-year-old female child presenting with developmental delay emphasizes the clinical relevance of cytogenetic diagnosis in the better management of genetic disorders. Application of subtelomeric FISH technique revealed the presence of interstitial telomeres and led to the ascertainment of partial trisomy for the distal 7p segment localized on the telomeric end of the short arm of chromosome 19. Whole-genome cytogenetic microarray-based analysis showed a mosaic 3.5 Mb gain at Xq21.1 besides the approximately 24.5 Mb gain corresponding to 7p15.3- > pter. The possible mechanisms of origin of the chromosomal rearrangement and the clinical relevance of trisomy for the genes lying in the critical regions are discussed.

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. Nonrandom chromosomal change (trisomy 11) in murine plasmacytomas induced by an ABL-MYC retrovirus.

    Science.gov (United States)

    Wiener, F; Coleman, A; Mock, B A; Potter, M

    1995-03-01

    Trisomy of chromosome 11 (Ts11) is the second most frequent nonrandom chromosomal change in murine plasmacytomas (PCTs). The frequency of Ts11 is significantly higher in PCTs induced in pristane-conditioned mice infected by Abelson-murine leukemia virus (52%) compared to those induced by pristane alone (8.1%). Although the significance of Ts11 in mouse plasmacytomagenesis is not clearly understood it is hypothesized that a gene or genes located on chromosome (Chr) 11 may specifically promote the development of PCTs in which both oncogenes, c-myc and v-abl, are abundantly expressed. To test this assumption we induced PCTs by three highly effective plasmacytomagenic retroviruses: ABL-MYC, J3V1, and RIM. Nearly 90% of PCTs that arose in BALB/c, (BALB/c x DBA/2N)F1, BALB/c-nu/nu, and 5-month-old SCID mice infected with ABL-MYC virus were trisomic for Chr 11. In contrast, < 10% of PCTs induced by J3V1 or RIM retroviral constructs encompassing either v-myc and v-raf or c-myc and v-Ha-ras oncogenes, respectively, contained Ts11. We have also investigated whether the entire Chr 11 or any particular subregion is preferentially duplicated in the process of ABL-MYC plasmacytomagenesis. By inducing PCTs in F1 heterozygous mice that are carriers of reciprocal translocations involving Chr 11 we found that the duplicated chromosomal region is located distal to the T4Dn breakpoint (11B5 band) on the telomeric segment of Chr 11. The regular duplication of this chromosomal segment strongly suggests the presence of a gene or genes whose amplification is of critical importance for v-abl associated murine plasmacytomagenesis. PMID:7867005

  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. No evidence of association between blastocyst aneuploidy and morphokinetic assessment in a selected population of poor-prognosis patients: a longitudinal cohort study.

    Science.gov (United States)

    Rienzi, L; Capalbo, A; Stoppa, M; Romano, S; Maggiulli, R; Albricci, L; Scarica, C; Farcomeni, A; Vajta, G; Ubaldi, F M

    2015-01-01

    Recent studies involving a limited number of patients have indicated a correlation between aneuploidy and various morphokinetic parameters during preimplantation development. The results among different groups, however, have been inconsistent in identifying the parameters that are able to predict chromosomal abnormalities. The aim of this study was to investigate whether aneuploidy of human blastocysts was detectable by specific morphokinetic parameters in patients at increased risk of aneuploidy because of advanced maternal age, history of unsuccessful IVF treatments, or both. A longitudinal cohort study was conducted using 455 blastocysts from 138 patients. Morphokinetic features of preimplantation development were detected in a timelapse incubator. Blastocysts were subjected to trophectodermal biopsy and comprehensive chromosomal screening. Analyses were conducted by means of logistic mixed-effects models, with a subject-specific intercept. No statistical correlation between 16 commonly detected morphokinetic characteristics of in-vitro embryo development and aneuploidy was found. Results suggest that morphokinetic characteristics cannot be used to select euploid blastocysts in poor-prognosis patients regarded as candidates for pre-implantation genetic screening. PMID:25458852

  8. 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.

  9. Elevated tolerance to aneuploidy in cancer cells: estimating the fitness effects of chromosome number alterations by in silico modelling of somatic genome evolution.

    Science.gov (United States)

    Valind, Anders; Jin, Yuesheng; Gisselsson, David

    2013-01-01

    An unbalanced chromosome number (aneuploidy) is present in most malignant tumours and has been attributed to mitotic mis-segregation of chromosomes. However, recent studies have shown a relatively high rate of chromosomal mis-segregation also in non-neoplastic human cells, while the frequency of aneuploid cells remains low throughout life in most normal tissues. This implies that newly formed aneuploid cells are subject to negative selection in healthy tissues and that attenuation of this selection could contribute to aneuploidy in cancer. To test this, we modelled cellular growth as discrete time branching processes, during which chromosome gains and losses were generated and their host cells subjected to selection pressures of various magnitudes. We then assessed experimentally the frequency of chromosomal mis-segregation as well as the prevalence of aneuploid cells in human non-neoplastic cells and in cancer cells. Integrating these data into our models allowed estimation of the fitness reduction resulting from a single chromosome copy number change to an average of ≈30% in normal cells. In comparison, cancer cells showed an average fitness reduction of only 6% (p = 0.0008), indicative of aneuploidy tolerance. Simulations based on the combined presence of chromosomal mis-segregation and aneuploidy tolerance reproduced distributions of chromosome aberrations in >400 cancer cases with higher fidelity than models based on chromosomal mis-segregation alone. Reverse engineering of aneuploid cancer cell development in silico predicted that aneuploidy intolerance is a stronger limiting factor for clonal expansion of aneuploid cells than chromosomal mis-segregation rate. In conclusion, our findings indicate that not only an elevated chromosomal mis-segregation rate, but also a generalised tolerance to novel chromosomal imbalances contribute to the genomic landscape of human tumours. PMID:23894657

  10. 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.

  11. Chronic up-regulation of the SHH pathway normalizes some developmental effects of trisomy in Ts65Dn mice.

    Science.gov (United States)

    Dutka, Tara; Hallberg, Dorothy; Reeves, Roger H

    2015-02-01

    Down Syndrome (DS) is a highly complex developmental genetic disorder caused by trisomy for human chromosome 21 (Hsa21). All individuals with DS exhibit some degree of brain structural changes and cognitive impairment; mouse models such as Ts65Dn have been instrumental in understanding the underlying mechanisms. Several phenotypes of DS might arise from a reduced response of trisomic cells to the Sonic Hedgehog (SHH) growth factor. If all trisomic cells show a similar reduced response to SHH, then up-regulation of the pathway in trisomic cells might ameliorate multiple DS phenotypes. We crossed Ptch1tm1Mps/+ mice, in which the canonical SHH pathway is expected to be up-regulated in every SHH-responsive cell due to the loss of function of one allele of the pathway suppressor, Ptch1, to the Ts65Dn DS model and assessed the progeny for possible rescue of multiple DS-related phenotypes. Down-regulation of Ptch produced several previously unreported effects on development by itself, complicating interpretation of some phenotypes, and a number of structural or behavioral effects of trisomy were not compensated by SHH signaling. However, a deficit in a nest-building task was partially restored in Ts;Ptch+/- mice, as were the structural anomalies of the cerebellum seen in Ts65Dn mice. These results extend the body of evidence indicating that reduced response to SHH in trisomic cells and tissues contributes to various aspects of the trisomic phenotype. PMID:25511459

  12. 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

  13. 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

  14. The influence of sterol metabolism upon radiation-induced aneuploidy of Drosophila melanogaster in the yeast-drosophila system

    International Nuclear Information System (INIS)

    The influence of sterol metabolism upon induced Drosophila melanogaster mutagenesis in an ecology-genetic yeast-drosophila system has been studied. The sterol deficit in fly organism has been created for account of using as food substrate for fremales of biomass of saccharomyces cerevisiae living cells of 9-2-PZ12 train with nyssup(r1) locus mutation which blocks the ergosterol synthesis. It has been found that the Drosophila females content on mutant yeast increases the frequency of losses and non discrepancy of X-chromosomes induced by X-radiation (1000 R). Addition into yeast biomass of 0.1 % cholesterol solution in 10 %-ethanol reduces the oocytes resistance to X-radiation up to control level. Possible hormonal and membrane mechanisms of increasing radiation-induced aneuploidy of Drosophila and the role of sterol metabolism in organism resistance to damaging factors are discussed

  15. 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.

  16. 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.

  17. 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

  18. Human endogenous retrovirus-FRD envelope protein (syncytin 2 expression in normal and trisomy 21-affected placenta

    Directory of Open Access Journals (Sweden)

    Handschuh Karen

    2008-01-01

    Full Text Available Abstract Human trophoblast expresses two fusogenic retroviral envelope proteins, the widely studied syncytin 1, encoded by HERV-W and the recently characterized syncytin 2 encoded by HERV-FRD. Here we studied syncytin 2 in normal and Trisomy 21-affected placenta associated with abnormal trophoblast differentiation. Syncytin 2 immunolocalization was restricted throughout normal pregnancy to some villous cytotrophoblastic cells (CT. During the second trimester of pregnancy, syncytin 2 was immunolocalized in some cuboidal CT in T21 placentas, whereas in normal placentas it was observed in flat CT, extending into their cytoplasmic processes. In vitro, CT isolated from normal placenta fuse and differentiate into syncytiotrophoblast. At the same time, syncytin 2 transcript levels decreased significantly with syncytiotrophoblast formation. In contrast, CT isolated from T21-affected placentas fused and differentiated poorly and no variation in syncytin 2 transcript levels was observed. Syncytin 2 expression illustrates the abnormal trophoblast differentiation observed in placenta of fetal T21-affected pregnancies.

  19. 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.

  20. 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.

  1. 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...

  2. 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 ...

  3. 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)

  4. 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...

  5. 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...

  6. 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.

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

    OpenAIRE

    El Khattabi, Laïla Allach; Rouillac-Le Sciellour, Christelle; Le Tessier, Dominique; Luscan, Armelle; Coustier, Audrey; Porcher, Raphael; Bhouri, Rakia; Nectoux, Juliette; Sérazin, Valérie; Quibel, Thibaut; Mandelbrot, Laurent; Tsatsaris, Vassilis; Vialard, François; Dupont, Jean-Michel

    2016-01-01

    Objective 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. Method After technical optimization of the multiplex PCR on mixtures of trisomic and euploid DNA, we performed a validation study on samples of plasma DNA ...

  8. Overlapping Trisomies for Human Chromosome 21 Orthologs Produce Similar Effects on Skull and Brain Morphology of Dp(16)1Yey and Ts65Dn Mice

    OpenAIRE

    Starbuck, John M; Dutka, Tara; Ratliff, Tabetha S.; Reeves, Roger H.; Richtsmeier, Joan T.

    2014-01-01

    Trisomy 21 results in gene-dosage imbalance during embryogenesis and throughout life, ultimately causing multiple anomalies that contribute to the clinical manifestations of Down syndrome. Down syndrome is associated with manifestations of variable severity (e.g., heart anomalies, reduced growth, dental anomalies, shortened life-span). Craniofacial dysmorphology and cognitive dysfunction are consistently observed in all people with Down syndrome. Mouse models are useful for studying the effec...

  9. 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; Friis-Hansen, Lennart; Jørgensen, Finn Stener

    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...... calculation programs to assess whether the screening efficacies for T13, T18, and T21 could be improved by using our locally estimated medians....

  10. 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...

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. Overlapping trisomies for human chromosome 21 orthologs produce similar effects on skull and brain morphology of Dp(16)1Yey and Ts65Dn mice.

    Science.gov (United States)

    Starbuck, John M; Dutka, Tara; Ratliff, Tabetha S; Reeves, Roger H; Richtsmeier, Joan T

    2014-08-01

    Trisomy 21 results in gene-dosage imbalance during embryogenesis and throughout life, ultimately causing multiple anomalies that contribute to the clinical manifestations of Down syndrome. Down syndrome is associated with manifestations of variable severity (e.g., heart anomalies, reduced growth, dental anomalies, shortened life-span). Craniofacial dysmorphology and cognitive dysfunction are consistently observed in all people with Down syndrome. Mouse models are useful for studying the effects of gene-dosage imbalance on development. We investigated quantitative changes in the skull and brain of the Dp(16)1Yey Down syndrome mouse model and compared these mice to Ts65Dn and Ts1Cje mouse models. Three-dimensional micro-computed tomography images of Dp(16)1Yey and euploid mouse crania were morphometrically evaluated. Cerebellar cross-sectional area, Purkinje cell linear density, and granule cell density were evaluated relative to euploid littermates. Skulls of Dp(16)1Yey and Ts65Dn mice displayed similar changes in craniofacial morphology relative to their respective euploid littermates. Trisomy-based differences in brain morphology were also similar in Dp(16)1Yey and Ts65Dn mice. These results validate examination of the genetic basis for craniofacial and brain phenotypes in Dp(16)1Yey mice and suggest that they, like Ts65Dn mice, are valuable tools for modeling the effects of trisomy 21 on development. PMID:24788405

  16. Genetically induced abnormal cranial development in human trisomy 18 with holoprosencephaly: comparisons with the normal tempo of osteogenic-neural development.

    Science.gov (United States)

    Reid, Shaina N; Ziermann, Janine M; Gondré-Lewis, Marjorie C

    2015-07-01

    Craniofacial malformations are common congenital defects caused by failed midline inductive signals. These midline defects are associated with exposure of the fetus to exogenous teratogens and with inborn genetic errors such as those found in Down, Patau, Edwards' and Smith-Lemli-Opitz syndromes. Yet, there are no studies that analyze contributions of synchronous neurocranial and neural development in these disorders. Here we present the first in-depth analysis of malformations of the basicranium of a holoprosencephalic (HPE) trisomy 18 (T18; Edwards' syndrome) fetus with synophthalmic cyclopia and alobar HPE. With a combination of traditional gross dissection and state-of-the-art computed tomography, we demonstrate the deleterious effects of T18 caused by a translocation at 18p11.31. Bony features included a single developmentally unseparated frontal bone, and complete dual absence of the anterior cranial fossa and ethmoid bone. From a superior view with the calvarium plates removed, there was direct visual access to the orbital foramen and hard palate. Both the eyes and the pituitary gland, normally protected by bony structures, were exposed in the cranial cavity and in direct contact with the brain. The middle cranial fossa was shifted anteriorly, and foramina were either missing or displaced to an abnormal location due to the absence or misplacement of its respective cranial nerve (CN). When CN development was conserved in its induction and placement, the respective foramen developed in its normal location albeit with abnormal gross anatomical features, as seen in the facial nerve (CNVII) and the internal acoustic meatus. More anteriorly localized CNs and their foramina were absent or heavily disrupted compared with posterior ones. The severe malformations exhibited in the cranial fossae, orbital region, pituitary gland and sella turcica highlight the crucial involvement of transcription factors such as TGIF, which is located on chromosome 18 and contributes

  17. A Cost-Effectiveness Analysis of First Trimester Non-Invasive Prenatal Screening for Fetal Trisomies in the United States.

    Directory of Open Access Journals (Sweden)

    Brandon S Walker

    Full Text Available Non-invasive prenatal testing (NIPT is a relatively new technology for diagnosis of fetal aneuploidies. NIPT is more accurate than conventional maternal serum screening (MSS but is also more costly. Contingent NIPT may provide a cost-effective alternative to universal NIPT screening. Contingent screening used a two-stage process in which risk is assessed by MSS in the first stage and, based on a risk cutoff, high-risk pregnancies are referred for NIPT. The objective of this study was to (1 determine the optimum MSS risk cutoff for contingent NIPT and (2 compare the cost effectiveness of optimized contingent NIPT to universal NIPT and conventional MSS.Decision-analytic model using micro-simulation and probabilistic sensitivity analysis. We evaluated cost effectiveness from three perspectives: societal, governmental, and payer.From a societal perspective, universal NIPT dominated both contingent NIPT and MSS. From a government and payer perspective, contingent NIPT dominated MSS. Compared to contingent NIPT, adopting a universal NIPT would cost $203,088 for each additional case detected from a government perspective and $263,922 for each additional case detected from a payer perspective.From a societal perspective, universal NIPT is a cost-effective alternative to MSS and contingent NIPT. When viewed from narrower perspectives, contingent NIPT is less costly than universal NIPT and provides a cost-effective alternative to MSS.

  18. Diaphragm myoclonus followed by generalised atonia in a patient with trisomy 4p: unusual semiology in an unusual condition.

    Science.gov (United States)

    Varley, James; Wehner, Tim; Sisodiya, Sanjay

    2015-12-01

    In this report, we describe a female patient with trisomy 4p, a rare genetic condition, with unusual seizure semiology. The patient is one of the oldest reported survivors with this condition. This semiology was noted while she was being monitored by inpatient video telemetry. We observed a series of myoclonic shoulder jerks, followed by hiccup-like episodes, and finally an atonic head drop. Corresponding ictal EEG showed semi-rhythmic high-amplitude slow waves with spikes superimposed over the frontotemporal areas. This semiology was confirmed as habitual by her parents. Subsequent hiccup-like episodes had no EEG correlate, and the head drop was again associated with semi-rhythmic high-amplitude slow waves and superimposed spikes, more prominent over the right hemisphere. In addition, we review the several cases in which hiccups have been associated with seizures and how this may relate to the neural pathways involved in the pathophysiology of hiccups. We believe the ictal hiccup-like episodes followed by atonia to be a seizure semiology that has not previously been documented. [Published with video sequence]. PMID:26620821

  19. Sacrococcygeal teratoma in a female newborn with clinical features of trisomy 13: a case report from Central Africa

    Directory of Open Access Journals (Sweden)

    Lubala TK

    2015-12-01

    Full Text Available Toni Kasole Lubala,1,2 Olivier Mukuku,1 Mick Pongombo Shongo,1,2 Augustin Mulangu Mutombo,1 Nina Lubala,1 Oscar Numbi Luboya,1 Prosper Lukusa-Tshilobo3 1Department of Paediatrics, Faculty of Medicine, 2Center for Human Genetics, Faculty of Medicine, University of Lubumbashi, Lubumbashi, 3Department of Paediatrics and Centre for Human Genetics, University Hospital, University of Kinshasa, Kinshasa, Democratic Republic of Congo Introduction: The objective of this report is to describe the first patient presenting clinical features of trisomy 13 in association with a sacrococcygeal teratoma. Case presentation: We present the case of a Congolese female infant born with bilateral cleft lip and palate, hypotelorism, microcephaly, and capillary hemangioma on her face. She presented with a large sacrococcygeal mass (15.0 cm ×12.0 cm ×5.0 cm with a cystic consistency and a positive transillumination. Conclusion: This observation suggests that overexpression of certain genes on chromosome 13 may lead to tumor formation from remnant cells of Hensen’s node. Keywords: Patau syndrome, Hensens’s Node, sacrococcygeal, teratoma  

  20. Epigenetic Dysregulation Observed in Monosomy Blastocysts Further Compromises Developmental Potential

    Science.gov (United States)

    Denomme, Michelle M.; McCallie, Blair R.; Parks, Jason C.; Schoolcraft, William B.; Katz-Jaffe, Mandy G.

    2016-01-01

    Epigenetic mechanisms such as DNA methylation regulate genomic imprinting and account for the distinct non-equivalence of the parental genomes in the embryo. Chromosomal aneuploidy, a major cause of infertility, distorts this highly regulated disparity by the presence or absence of chromosomes. The implantation potential of monosomy embryos is negligible compared to their trisomy counterparts, yet the cause for this is unknown. This study investigated the impact of chromosomal aneuploidy on strict epigenetically regulated domains, specifically imprinting control regions present on aneuploid chromosomes. Donated cryopreserved human IVF blastocysts of transferable quality, including trisomy 15, trisomy 11, monosomy 15, monosomy 11, and donor oocyte control blastocysts were examined individually for DNA methylation profiles by bisulfite mutagenesis and sequencing analysis of two maternally methylated imprinting control regions (ICRs), SNRPN (15q11.2) and KCNQ1OT1 (11p15.5), and one paternally methylated imprinting control region, H19 (11p15.5). Imprinted genes within the regions were also evaluated for transcript abundance by RT-qPCR. Overall, statistically significant hypermethylated and hypomethylated ICRs were found in both the trisomy and monosomy blastocysts compared to controls, restricted only to the chromosome affected by the aneuploidy. Increased expression was observed for maternally-expressed imprinted genes in trisomy blastocysts, while a decreased expression was observed for both maternally- and paternally-expressed imprinted genes in monosomy blastocysts. This epigenetic dysregulation and altered monoallelic expression observed at imprinting control regions in aneuploid IVF embryos supports euploid embryo transfer during infertility treatments, and may specifically highlight an explanation for the compromised implantation potential in monosomy embryos. PMID:27271036

  1. Quantification of the DNA content of structurally abnormal X chromosomes and X chromosome aneuploidy using high resolution bivariate flow karyotyping.

    Science.gov (United States)

    Trask, B; van den Engh, G; Nussbaum, R; Schwartz, C; Gray, J

    1990-01-01

    Quantification of the Hoechst and chromomycin A3 fluorescence intensities of mitotic human chromosomes isolated from karyotypically normal and abnormal cells was performed with a dual beam flow cytometer. The resultant flow karyotypes contain information about the relative DNA content and base composition of chromosomes and their relative frequencies in the mitotic cell sample. The relative copy number of X and Y chromosomes was determined for 38 normal males and females and 6 cell lines with X or Y chromosome aneuploidy. Flow karyotype diagnoses corresponded with conventional cytogenetic results in all cases. We show that chromosome DNA content can be derived from peak position in Hoechst vs. chromomycin flow karyotypes. These values are linearly related to propidium iodide staining intensity as measured with flow cytometry and to the binding of gallocyanin chrome alum to phosphate groups as measured with slide-based scanning photometry. Cell lines with deleted or dicentric X chromosomes ranging in length from 0.53 to 1.95 times normal were analyzed by using flow cytometry. The measured difference in DNA content between a normal X and each of the structurally abnormal chromosomes was linearly correlated to the difference predicted from cytogenetics and/or probe analyses. Deletions of 3-5 Mb, which were at and below the detection limits of conventional cytogenetics, could be quantified by flow karyotyping in individuals with X-linked diseases such as Duchenne muscular dystrophy, choroideremia, and ocular albinism/ichthyosis. The results show that the use of flow karyotyping to quantify the size of restricted regions of the genome can complement conventional cytogenetics and other physical mapping techniques in the study of genetic disorders. PMID:2106419

  2. 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.

  3. The influence of fetal sex in screening for trisomy 21 by fetal nuchal translucency, maternal serum free beta-hCG and PAPP-A at 10-14 weeks of gestation.

    Science.gov (United States)

    Spencer, K; Ong, C Y; Liao, A W; Papademetriou, D; Nicolaides, K H

    2000-08-01

    In a study of 2923 normal pregnancies and 203 pregnancies affected by trisomy 21 we have shown a significant difference in the median MoM of the markers: fetal nuchal translucency, maternal serum free beta-hCG and PAPP-A in the presence of a female fetus compared with a male fetus. For maternal serum free beta-hCG levels are higher by 15% if the fetus is chromosomally normal and by 11% if the fetus has trisomy 21. For maternal serum PAPP-A the levels in chromosomally normal fetuses are 10% higher in the presence of a female fetus and 13% higher if the fetus has trisomy 21. In contrast, fetal nuchal translucency is 3-4% lower in both chromosomally normal and trisomy 21 female fetuses. The consequence of such changes when screening for trisomy 21 will be a reduction in the detection rate in female fetuses by a factor of 1-2%. Correction of risk algorithms for fetal sex, however, is probably not feasible, since ultrasound detection of fetal sex is only 70-90% accurate in the 10-14 week period. PMID:10951481

  4. 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

  5. Genetic Disorders

    Science.gov (United States)

    ... 21 (Down syndrome) . Other trisomies include trisomy 13 (Patau syndrome) and trisomy 18 (Edwards syndrome) . Monosomy is ... which there is an extra chromosome. Trisomy 13 (Patau Syndrome): A genetic disorder that causes serious heart ...

  6. 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

    Science.gov (United States)

    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 laryngoscope (FOL). A fiberoptic scope and any size of a laryngoscope blade can be easily assembled in the operating room. The FOL may be a useful device in the setting of difficult paediatric intubation. PMID:27366452

  7. Comparative Studies of the Chromosomal Arrangement in the C-Metaphase Between Normal Karyotype and Trisomy-21

    Directory of Open Access Journals (Sweden)

    D.D. Farhud

    1987-07-01

    Full Text Available Human chromosomes in amnion cells and lymphocytes with normal karyotype and in lymphocytes with pathological karyotype (2n=47, +21 were compared as to their position in the metaphase. None of the collectives showed sex differences. Measurement of the radial distances revealed more peripheral position of the majority of large chromosomes. The satellite-carrying chromosomes of the D group always had a central position in the mitosis. The chromosomes of the groups D, E, F and G were closest to the centre; with the exception of chromosome 18 which was peripheral in all three collectives. For the male probands, the y-chromosome was shown in all three collectives to have a smaller radial distance than the x-chromosome. A typical distribution was found for the radial and homologue distances for the trisomic cells, two of them had a very large radial distance, the third a value corresponding to its size. For the homolarger measurements hereby the distribution is quite independent of parental source. Comparison of the groups showed no differences either between normal and trisomy cells or between the different cell types. Examination of chromosomes 6 and 15 proved conclusively that the chromosomes are not particularly orientated in the c-metaphase regarding the position of short and long arm. A preferential combination of particular satellite carrying chromosomes leads to the frequent fusions of chromosomes 13 and 14, or 14 and 21. Equally, no preferential association could be demonstrated of the chromosome 21 and the chromosomes with large heterochromatin blocks in the centromere region (chromosomes 1 and 9. The distances were of the same order of magnitude as those between 21 and chromosome 6, a submetacentric chromosome without a marked heterochromatin region. Both latter observations are of specific importance for genetic councelling of couples after birth of a child with a de Novo chromosome aberration asking for the recurrence risk.

  8. GenEx: nízkonákladový systém pro hodnocení chromozomových aneuploidií v nízkofrekvenčních mozaikách

    Czech Academy of Sciences Publication Activity Database

    Schier, Jan; Kovář, Bohumil; Kuneš, Michal; Kočárek, E.; Tesner, P.; Zemčík, P.; Dubská, M.; Honec, P.; Číp, P.

    Praha: -, 2014. s. 83-83. [Genetická konference GSGM 2014. 24.09.2014-26.09.2014, Praha] R&D Projects: GA TA ČR TA01010931 Institutional support: RVO:67985556 Keywords : image processing * microscopy * cytology * chromosome aneuploidies Subject RIV: JC - Computer Hardware ; Software http://library.utia.cas.cz/separaty/2014/ZOI/schier-0438888.pdf

  9. 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.

  10. Insulin growth factor 1 receptor expression is associated with NOTCH1 mutation, trisomy 12 and aggressive clinical course in chronic lymphocytic leukaemia.

    Directory of Open Access Journals (Sweden)

    Francesco Maura

    Full Text Available IGF1R is emerging as an important gene in the pathogenesis of many solid and haematological cancers and its over-expression has been reported as frequently associated with aggressive disease and chemotherapy resistance. In this study we performed an investigation of the role of IGF1R expression in a large and representative prospective series of 217 chronic lymphocytic leukaemia (CLL patients enrolled in the multicentre O-CLL1 protocol (clinicaltrial.gov #NCT00917540. High IGF1R gene expression was significantly associated with IGHV unmutated (IGHV-UM status (p<0.0001, high CD38 expression (p<0.0001, trisomy 12 (p<0.0001, and del(11(q23 (p=0.014. Interestingly, higher IGF1R expression (p=0.002 characterized patients with NOTCH1 mutation (c.7541_7542delCT, identified in 15.5% of cases of our series by next generation sequencing and ARMS-PCR. Furthermore, IGF1R expression has been proven as an independent prognostic factor associated with time to first treatment in our CLL prospective cohort. These data suggest that IGF1R may play an important role in CLL biology, in particular in aggressive CLL clones characterized by IGHV-UM, trisomy 12 and NOTCH1 mutation.

  11. Insulin growth factor 1 receptor expression is associated with NOTCH1 mutation, trisomy 12 and aggressive clinical course in chronic lymphocytic leukaemia.

    Science.gov (United States)

    Maura, Francesco; Mosca, Laura; Fabris, Sonia; Cutrona, Giovanna; Matis, Serena; Lionetti, Marta; Agnelli, Luca; Barbieri, Marzia; D'Anca, Marianna; Manzoni, Martina; Colombo, Monica; Massucco, Carlotta; Reverberi, Daniele; Gentile, Massimo; Recchia, Anna Grazia; Bossio, Sabrina; Ilariucci, Fiorella; Musolino, Caterina; Di Raimondo, Francesco; Cortelezzi, Agostino; Morabito, Fortunato; Ferrarini, Manlio; Neri, Antonino

    2015-01-01

    IGF1R is emerging as an important gene in the pathogenesis of many solid and haematological cancers and its over-expression has been reported as frequently associated with aggressive disease and chemotherapy resistance. In this study we performed an investigation of the role of IGF1R expression in a large and representative prospective series of 217 chronic lymphocytic leukaemia (CLL) patients enrolled in the multicentre O-CLL1 protocol (clinicaltrial.gov #NCT00917540). High IGF1R gene expression was significantly associated with IGHV unmutated (IGHV-UM) status (p<0.0001), high CD38 expression (p<0.0001), trisomy 12 (p<0.0001), and del(11)(q23) (p=0.014). Interestingly, higher IGF1R expression (p=0.002) characterized patients with NOTCH1 mutation (c.7541_7542delCT), identified in 15.5% of cases of our series by next generation sequencing and ARMS-PCR. Furthermore, IGF1R expression has been proven as an independent prognostic factor associated with time to first treatment in our CLL prospective cohort. These data suggest that IGF1R may play an important role in CLL biology, in particular in aggressive CLL clones characterized by IGHV-UM, trisomy 12 and NOTCH1 mutation. PMID:25786252

  12. Analytic device including nanostructures

    KAUST Repository

    Di, Fabrizio, E.

    2015-07-02

    A device for detecting an analyte in a sample comprising: an array including a plurality of pixels, each pixel including a nanochain comprising: a first nanostructure, a second nanostructure, and a third nanostructure, wherein size of the first nanostructure is larger than that of the second nanostructure, and size of the second nanostructure is larger than that of the third nanostructure, and wherein the first nanostructure, the second nanostructure, and the third nanostructure are positioned on a substrate such that when the nanochain is excited by an energy, an optical field between the second nanostructure and the third nanostructure is stronger than an optical field between the first nanostructure and the second nanostructure, wherein the array is configured to receive a sample; and a detector arranged to collect spectral data from a plurality of pixels of the array.

  13. A prospective study evaluating the performance of first trimester combined screening for trisomy 21 using repeated sampling of the maternal serum markers PAPP-A and free β-hCG

    DEFF Research Database (Denmark)

    Ekelund, Charlotte Kvist; Wright, Dave; Ball, Susan;

    2012-01-01

    To prospectively evaluate the performance of first-trimester combined screening for trisomy 21 using the biochemical markers pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (free β-hCG) obtained before and at the time of the nuchal translucency (NT) scan....

  14. Aneuploidy in stem cells

    NARCIS (Netherlands)

    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 real

  15. Effect of sterol metabolism in the yeast-Drosophila system on the frequency of radiation-induced aneuploidy in the Drosophila melanogaster oocytes

    International Nuclear Information System (INIS)

    The effect of sterol metabolism on induced mutagenesis of Drosophila melanogaster was studied in the ecogenetic system of yeast-Drosophila. Sterol deficiency was created in Drosophila by using the biomass of live cells of Saccharomyces cerevisiae strain 9-2-P712 till mutation in locus nys/sup r1/ blocking the synthesis of ergosterol as the food. It was found that rearing of Drosophila females on the mutant yeast increases the frequency of loss and nondisjunction of X chromosomes induced in mature oocytes by X rays (1000 R). Addition of 0.1% of cholesterol solution in 10% ethanol to the yeast biomass restores the resistance of oocyte to X irradiation to the control level. The possible hormonal effect on membrane leading to increased radiation-induced aneuploidy in Drosophila and the role of sterol metabolism in determining the resistance to various damaging factors are discussed

  16. Trisomy 13 (Patau Syndrome)

    OpenAIRE

    Masoud Poureisa

    2009-01-01

    "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 "nHypotel...

  17. Maternal uniparental disomy for human chromosome 14, due to loss of a chromosome 14 from somatic cells with t(13; 14) trisomy 14

    Energy Technology Data Exchange (ETDEWEB)

    Antonarakis, S.E.; Blouin, J.L.; Maher, J.; Avramopoulos, D.; Thomas, G.; Talbot, C.C. Jr. (Johns Hopkins Univ., Baltimore (United States))

    1993-06-01

    Uniparental disomy (UPD) for particular chromosomes is increasingly recognized as a cause of abnormal phenotypes in humans. The authors recently studied a 9-year-old female with a de novo Robertsonian translocation t(13;14), short stature, mild developmental delay, scoliosis, hyperextensible joints, hydrocephalus that resolved spontaneously during the first year of life, and hyperchloesterolemia. To determine the parental origin of chromosomes 13 and 14 in the proband, they have studied the genotypes of DNA polymorphic markers due to (GT)n repeats in the patient and her parents' blood DNA. The genotypes of markers D14S43, D14S45, D14S49, and D14S54 indicated maternal UPD for chromosome 14. There was isodisomy for proximal markers and heterodisomy for distal markers, suggesting a recombination event on maternal chromosomes 14. In addition, DNA analysis first revealed -- and subsequent cytogenetic analysis confirmed -- that there was mosaic trisomy 14 in 5% of blood lymphocytes. There was normal (biparental) inheritance for chromosome 13, and there was no evidence of false paternity in genotypes of 11 highly polymorphic markers on human chromosome 21. Two cases of maternal UPD for chromosome 14 have previously been reported, one with a familial rob t(13;14) and the other with a t(14;14). There are several similarities among these patients, and a [open quotes]maternal UPD chromosome 14 syndrome[close quotes] is emerging; however, the contribution of the mosaic trisomy 14 to the phenotype cannot be evaluated. The study of de novo Robertsonian translocations of the type reported here should reveal both the extent of UPD in these events and the contribution of particular chromosomes involved in certain phenotypes. 33 refs., 3 figs., 1 tab.

  18. Prenatal Diagnosis and Postnatal Followup of Partial Trisomy 13q and Partial Monosomy 10p: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Yuan Wei

    2012-01-01

    Full Text Available We report prenatal diagnosis and postnatal findings of a fetus with partial trisomy of 13q21.33-qter and partial monosomy of 10p15.3-pter. The mother is a known carrier of a balanced translocation, t(10;13(p15.3;q21.33, ascertained by history of one miscarriage and two neonatal deaths. The fetal karyotyping on cultured amniocytes showed 46,XX,der(10t(10;13(p15.3;q21.33. Oligonucleotide array comparative genomic hybridization (aCGH defined a 2.339 Mb distal deletion at 10p15.3 (chr10:126,161–2,465,089 and a 46.344 Mb duplication of 13q21.33–q34 (chr13:67,779,708–114,123,540. Ultrasound examination showed polydactyly and polyhydramnios in the fetus. After genetic counseling, the mother decided to continue the pregnancy, and follow-up ultrasound monitoring found no further abnormalities. A girl was delivered at 37+6 weeks of gestation and was transferred to the intensive care unit for intermittent convulsions within 26 hours. She was diagnosed with neonatal hypoxic ischemic encephalopathy and experienced several episodes of apnea in the following month. Her birth weight was 2900 g (10–25th centile and at five months was 5500 g (5–10th centile. She had dysmorphic features and mild psychomotor retardation. A review of the literature found three previously reported cases with similar compound 10p/13q abnormalities. We discuss a two-step approach to assess fetal viability and phenotype using genomic information from partial trisomy and monosomy.

  19. Detection of fetal cell-free DNA in maternal plasma for Down syndrome, Edward syndrome and Patau syndrome of high risk fetus

    Science.gov (United States)

    Ke, Wei-Lin; Zhao, Wei-Hua; Wang, Xin-Yu

    2015-01-01

    Objective: The study aimed to validate the efficacy of detection of fetal cell-free DNA in maternal plasma of trisomy 21, 18 and 13 in a clinical setting. Methods: A total of 2340 women at high risk for Down syndrome based on maternal age, prenatal history or a positive sesum or sonographic screening test were offered prenatal noninvasive aneuploidy test. According to the prenatal noninvasive aneuploidy test, the pregnant women at high risk were offered amniocentesis karyotype analysis and the pregnant at low risk were followed up to make sure the newborn outcome. Results: The prenatal noninvasive aneuploidy test was positive for trisomy 21 in 17 cases, for trisomy 18 in 6 cases and for trisomy 13 in 1 case, which of all were confirmed by karyotype analysis. Newborns of low risk gestational woman detected by prenatal noninvasive aneuploidy for trisomy 21, 18, 13 were followed up and no one was found with trisomy. Conclusions: The prenatal noninvasive aneuploidy test is highly accurate for detection of trisomy 21, 18 and 13, which can be considered as a practical alternative for traditional invasive diagnostic procedures. PMID:26309618

  20. Dandy-Walker malformations in a case of partial trisomy 9p (p12.1→pter due to maternal translocation t(9;12(p12.1;p13.3

    Directory of Open Access Journals (Sweden)

    Vundinti Babu Rao

    2007-01-01

    Full Text Available We describe a five-year-old proband presented with Dandy-Walker malformations, right microopthalmia, hamstring contractures, undescended testis with absence of testis in right scrotum in addition to typical trisomy 9p clinical features. Routine cytogenetic studies with GTG - banding showed 46,XY,der(12t(9;12 (p12;q13.3,mat karyotype (trisomy 9p. Chromosomal analysis of the father was normal and phenotypically normal mother had 46,XX,t(9;12(p12;q13 karyotype. Fluorescence in situ hybridization analysis with single copy probes bA5OIA2 (9p11.2, bA562M8 (12p12.1 and centromere probes (9 showed break point at 9p12.1 region. The gene dosage effect of Chromosome 9p along with environmental factors might be associated with Dandy- Walker malformations in the patient.

  1. Two cases of partial trisomy 8p and partial monosomy 21q in a family with a reciprocal translocation (8;21)(p21.1;q22.3).

    OpenAIRE

    Plomp, A.S.; Engelen, J.J.; Albrechts, J C; de Die-Smulders, C E; Hamers, A J

    1998-01-01

    We report on two mentally retarded adults with an unbalanced karyotype resulting from a familial balanced translocation between chromosomes 8 and 21, t(8;21)(p21.1;q22.3). This translocation has not been reported before. Both patients had partial trisomy 8p and partial monosomy 21q. Fluorescence in situ hybridisation (FISH) was used to determine the chromosomal breakpoints more precisely. The first patient showed mild mental retardation and facial dysmorphism, slightly resembling the earlier ...

  2. Correlation between Fetal Pyelectasis and Chromosome Aneuploidy: a Retrospective Study of 122 Cases%122例胎儿肾盂扩张与染色体非整倍体的关联性分析

    Institute of Scientific and Technical Information of China (English)

    商梅娇; 周祎; 鲁云涯; 陈涌珍; 陈宝江; 方群

    2013-01-01

    [Objective] To explore the correlation between fetal pyelectasis and aneuploidy. [Methods] A retrospective study of the karyotypes and delivery outcomes of selected 122 cases with fetal pyelectasis. Invasive prenatal procedures (amniocentesis or cordocentesis) were performed on all 122 patients with ultrasound guidance. [Results] Among the 122 fetal karyotypes, 87.7% (107/ 122) were normal karyotype, 4.9% (6/122) chromosomal abnormality and 7.4% (9/122) chromosomal polymorphism. All the cases were divided into four groups, Group Ⅰ (67 cases) with isolated pyelectasis, Group Ⅱ (34 cases) in association with one soft marker, Group Ⅲ (7 cases) complicated with two or more soft markers and Group Ⅳ (14 cases) accompanied with fetal structural malformation. From Group Ⅰ to Ⅳ , there were 94% (63 cases), 82.4% (28 cases), 100% (7 cases), and 64.3% (9 cases) with normal karyotypes, respectively; 4.5% (3 cases), 17.6% (6 cases), none case, and none case with chromosomal polymorphism; 1.5% (1 case), none case, none case, and 35.7% (5 cases, including 3 Down syndrome, 2 other abnormal karyotypes) with abnormal karyotypes. The 107 successfully followed-up newborns, including 87 boys and 20 girls, made the sexy ratio 4.35;1 (boy: girl). Eleven cases terminated pregnancy. In the 96 alive cases, 4 newborns were delivered prematurely, 92 were termly, 35 eutocia, and 61 cesarean; the average born gestational weeks was 39.1 weeks. Surgeries were carried out on 10 newborns because of hydronephrosis without relieving or exacerbation. [Conclusion] Isolated pyelectasis should not be a direct indication of invasive prenatal procedures. However, when fetal pyelectasis is accompanied with other soft markers or fetal structural malformation, invasive prenatal procedures for aneuploidy is advocated. The urinary system function should be followed up closely after birth, and the majority of the pyelectasis fetuses have satisfying prognosis.%[目的]探讨胎儿肾盂扩张在染

  3. Jacobsen and Beckwith-Wiedemann syndromes in a child with mosaicism for partial 11pter trisomy and partial 11qter monosomy.

    Science.gov (United States)

    Putoux, Audrey; Labalme, Audrey; André, Jean-Marie; Till, Marianne; Schluth-Bolard, Caroline; Berard, Jérôme; Bertrand, Yves; Edery, Patrick; Putet, Guy; Sanlaville, Damien

    2013-02-01

    We report on a child with Jacobsen syndrome (JBS, OMIM 147791) and abnormalities consistent with Beckwith-Wiedemann syndrome (BWS, OMIM 130650). The constitutional karyotype was apparently normal, but FISH analysis with probes specific for the short and long arms of chromosome 11 found 11qter deletion with 11pter trisomy in 80% of the cells studied. Array-CGH identified breakpoints in the 11p15.3 and 11q24.1 regions consistent with Jacobsen and Beckwith-Wiedemann syndromes. We suggest that this chromosome imbalance results from a pericentric inversion of chromosome 11 inherited from the father, with mosaicism resulting from meiotic recombination of a paternal inversion followed by mitotic recombination during the first embryonic divisions. This hypothesis is supported by the results of microsatellite marker analysis. Three previous cases of pericentric inversion and recombination of chromosome 11 have been reported. Our case is unusual in that it combines the Jacobsen and Beckwith-Wiedemann syndromes with mosaicism. PMID:23322614

  4. Myoclonic epilepsy of late onset in trisomy 21 Epilepsia mioclônica de início tardio na trissomia 21

    Directory of Open Access Journals (Sweden)

    Lm. Li

    1995-12-01

    Full Text Available We report the case of a patient with trisomy 21 (T21 with late onset epilepsy. The electro-clinical features were of myoclonic jerks on awakening and generalised tonic clonic seizures, with generalised spike and wave on EEG, and a progressive dementia. As familial Alzheimer's dementia and progressive myoclonic epilepsy (Unverricht-Lundborg type are both linked to the chromosome 21, this case may represent a distinct progressive myoclonic epilepsy related to T21.Pacientes com trissomia do cromossoma 21 (T21, com o passar dos anos, são propensos a desenvolver crises epilépticas parciais concomitantes ao aparecimento de degeneração cerebral do tipo Alzheimer. Pacientes com T21 e demência parecem ter risco maior de apresentarem crises epilépticas que outros pacientes com degeneração cerebral do tipo Alzheimer. O caso relatado é de um paciente com T21 com epilepsia de início tardio. A história clínica consiste de crises mioclônicas ao despertar, ocasionais crises generalizadas tônico-clônicas, demência e ponta onda generalisada no EEG. Demência do tipo Alzheimer familial é ligada ao cromossoma 21, bem como epilepsia mioclônica progressiva (tipo Unverricht-Lundborg. Isto sugere que este caso possa representar um tipo distinto de epilepsia mioclônica progressiva, ligado ao cromossoma 21.

  5. Medical and Ethical Considerations Related to Viable Fetuses with Trisomy 13 in the 36th Week of Pregnancy--a Review of the Literature.

    Science.gov (United States)

    Pawelec, Małgorzata; Dżugalik, Małgorzata; Pietras, Jolanta; Bełza, Łukasz; Latkowski, Łukasz

    2015-01-01

    Patau syndrome was first described in 1960 as a group of birth defects caused by trisomy of chromosome 13 (T13). Providing accurate information and relevant reproductive genetic counseling that would allow parents to make informed decisions is not easily accomplished because of the limited information available prenatally. Only 1/3 of all cases of T13 are diagnosed prenatally, which means it cannot be expected that most cases will be detected early in pregnancy, that the parents will decide to terminate the pregnancy, and that difficulties will be avoided. There is no good prenatal screening for T13, and there are many kinds and degrees of anomalies. About 60% of cases are first detected in the second trimester, and life expectancy is difficult to predict. When patients choose not to terminate pregnancy, or when the pregnancy has progressed to a viable gestational age, pregnancy termination is no longer an option. Also, nowadays 12% of couples choose to continue pregnancy following chromosomal confirmation of a suspected T13. The aim of this work is to eludicate for health care providers what problems they are likely to face in the care of children with T13 and in contact with their parents. It is crucial for the management of each case to discuss neonatal procedures of resuscitation, alternatives to aggressive resuscitation, the possibilities for correcting some of the defects, and to be prepared to guide the parents through the trauma of having a child with a lethal defect. PMID:26768645

  6. NON-INVASIVE PRENATAL DIAGNOSIS: A REVIEW

    Directory of Open Access Journals (Sweden)

    Madhusudan Dey, Sumita Agarwal and Sumedha Sharma

    2013-04-01

    Full Text Available ABSTRACT: Aneuploidies are one of the important causes of perinatal morbidity and mortality. Initially screening for aneuploidies started with maternal age risk estimation. Later on, serum testing for biochemical markers and ultrasound markers were added. Women detected to be at high risk for aneuploidies were offered invasive testing. Recently, various methods including non-invasive prenatal testing (NIPT by analysis of cell-free fetal DNA (cffDNA in maternal blood has shown promise for highly accurate detection of common fetal autosomal trisomies. Incorporating these new non-invasive technologies into clinical practice will impact the current prenatal screening paradigm for fetal aneuploidy, in which genetic counselling plays an integral role. The advantage of the technique being elimination of risks such as miscarriage associated with invasive diagnostic procedures. But then this new technique has its own set of technical limitations and ethical issues at present and further research is required before implementation. Data was obtained through a literature search via Pubmed and Google as well as detailed search of our library database.

  7. High Fat Diet Induced Developmental Defects in the Mouse: Oocyte Meiotic Aneuploidy and Fetal Growth Retardation/Brain Defects

    OpenAIRE

    Luzzo, Kerri M.; WANG Qiang; Purcell, Scott H.; Chi, Maggie; Jimenez, Patricia T.; Grindler, Natalia; Schedl, Tim; Moley, Kelle H.

    2012-01-01

    Background Maternal obesity is associated with poor outcomes across the reproductive spectrum including infertility, increased time to pregnancy, early pregnancy loss, fetal loss, congenital abnormalities and neonatal conditions. Furthermore, the proportion of reproductive-aged woman that are obese in the population is increasing sharply. From current studies it is not clear if the origin of the reproductive complications is attributable to problems that arise in the oocyte or the uterine env...

  8. Mitotic defects lead to pervasive aneuploidy and accompany loss of RB1 activity in mouse LmnaDhe dermal fibroblasts.

    Directory of Open Access Journals (Sweden)

    C Herbert Pratt

    Full Text Available BACKGROUND: Lamin A (LMNA is a component of the nuclear lamina and is mutated in several human diseases, including Emery-Dreifuss muscular dystrophy (EDMD; OMIM ID# 181350 and the premature aging syndrome Hutchinson-Gilford progeria syndrome (HGPS; OMIM ID# 176670. Cells from progeria patients exhibit cell cycle defects in both interphase and mitosis. Mouse models with loss of LMNA function have reduced Retinoblastoma protein (RB1 activity, leading to aberrant cell cycle control in interphase, but how mitosis is affected by LMNA is not well understood. RESULTS: We examined the cell cycle and structural phenotypes of cells from mice with the Lmna allele, Disheveled hair and ears (Lmna(Dhe. We found that dermal fibroblasts from heterozygous Lmna(Dhe (Lmna(Dhe/+ mice exhibit many phenotypes of human laminopathy cells. These include severe perturbations to the nuclear shape and lamina, increased DNA damage, and slow growth rates due to mitotic delay. Interestingly, Lmna(Dhe/+ fibroblasts also had reduced levels of hypophosphorylated RB1 and the non-SMC condensin II-subunit D3 (NCAP-D3, a mitosis specific centromere condensin subunit that depends on RB1 activity. Mitotic check point control by mitotic arrest deficient-like 1 (MAD2L1 also was perturbed in Lmna(Dhe/+ cells. Lmna(Dhe/+ fibroblasts were consistently aneuploid and had higher levels of micronuclei and anaphase bridges than normal fibroblasts, consistent with chromosome segregation defects. CONCLUSIONS: These data indicate that RB1 may be a key regulator of cellular phenotype in laminopathy-related cells, and suggest that the effects of LMNA on RB1 include both interphase and mitotic cell cycle control.

  9. Cytogenetic and molecular analysis of a ring (21) in a patient with partial trisomy 21 and megakaryocytic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Palmer, C.G.; Blouin, J.L.; Bull, M.J. [Indiana Univ. School of Medicine, Indianapolis, IN (United States)]|[Univ. of Geneva Medical School, Geneva (Switzerland)] [and others

    1995-07-17

    We describe a patient with an asymmetric double ring 21 in mosaic form, 45,XX,-21/46,X,-21,+r(21), who has limited manifestations of Down syndrome and who developed acute myelofibrosis and megakaryocytic leukemia (AMKL), FAB M7, a hematologic disorder particularly common in Down syndrome patients. In situ hybridization studies, gene dosage, and DNA polymorphism analysis showed that the ring chromosome carries a duplicated region which extends from D21S406 on the centromeric side and includes marker D21S3 on the telomeric side. FISH studies indicate two sizes of ring 21 in the patient. The origin of the supernumerary chromosome 21 in the proband was paternal; furthermore, the r(21) probably was formed postzygotically. Included in the duplicated segment are the candidate genes for leukemia AML-1, ETS, and ERG. The potential significance of disomic homozygosity of loci on 21q in M7 megakaryocytic leukemia is discussed. 35 refs., 6 figs., 6 tabs.

  10. Cytogenetic and molecular analysis of a ring (21) in a patient with partial trisomy 21 and megakaryocytic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Palmer, C.G.; Bull, M.; Breitfeld, P. [Indiana Univ., Indianapolis, IN (United States)] [and others

    1994-09-01

    We describe a patient with an asymmetrical double ring 21 in mosaic form, 45,XX, -21/46,XX, -21, +r(21) (q22.11{yields}p11.2::q11.1{yields}q22.3), who has limited manifestations of Down`s syndrome and who developed acute myelofibrosis and megakaryocytic leukemia (AMKL), M7, a hematologic disorder particularly common in Down`s syndrome patients. In situ hybridization studies (gene dosage and DNA polymorphism analysis) show that the ring chromosome carries a duplicated region which extends from D21S258 on the centromeric side and includes marker D21S1245 on the telomeric side, but does not include the region from PFKL and ITGB2 through the telomere. FISH studies indicate two sizes of ring 21 in the patient. The origin of the supernumerary chromosome 21 in the proband was paternal; furthermore, the r(21) was probably formed post-zygotically. Included in the duplicated segment are the candidate genes for leukemia AML-1, ETS2 and ERG. If disomic homozygosity is important in the development of AMKL in the proband, the gene responsible maps either between the centromere and D21S11 or between D21S1239 and D21S1245.

  11. Le diagnostic anténatal de la trisomie 21 par l'hybridation in situ en fluorescence (FISH): à propos des premiers tests réalisés au Maroc

    Science.gov (United States)

    Lamzouri, Afaf; Natiq, Abdelhafid; Tajir, Mariam; Sendid, Mohamed; Sefiani, Abdelaziz

    2012-01-01

    Introduction Le but de cette étude était de présenter les premiers résultats de diagnostic anténatal de la trisomie 21 par la technique d'hybridation in situ en fluorescence (FISH) au Maroc et discuter son intérêt dans le diagnostic rapide de cette aneuploïdie. Méthodes Ce travail a été réalisé chez 23 femmes avec des grossesses à haut risque de trisomie 21. La moyenne d’âge des gestantes étaient de 37,43 ans avec des extrêmes de 21 et 43 ans. Toutes étaient musulmanes mariées, mariage légitimé par la Charia, dont trois mariages consanguins, sauf une originaire de la République Démocratique du Congo qui était chrétienne et concubine. La majorité des femmes étaient fonctionnaires et avaient un niveau de scolarisation moyen à élevé. Toutes les patientes ont bénéficié d'une consultation de génétique médicale au cours de laquelle il leur a été donné des informations sur la technique, son intérêt et ses limites. Il s'agit de femmes enceintes qui avaient soit un âge maternel élevé ou des signes d'appel échographiques et/ ou biochimiques. Une des patientes était porteuse d'une translocation robertsonienne t(14;21) équilibrée. Une amniocentèse a été réalisée chez toutes les gestantes et aucun avortement n'a était induit par ce geste invasif. L’âge gestationnel moyen à la première consultation était de 14 semaines d'aménorrhée (SA) et à l'amniocentèse était de 16 SA et 5 jours. L'analyse FISH a été réalisée, après consentement des couples, sur des cellules non cultivées à partir des échantillons de liquides amniotiques, en utilisant des sondes spécifiques du chromosome 21. Résultats Parmi les 23 patientes qui ont bénéficiées d'un diagnostic anténatal de la trisomie 21 par la technique FISH, nous avons pu rassurer 21 d'entre elles, et nous avons détecté deux cas de trisomie 21 fœtal. Conclusion La technique FISH permet un diagnostic anténatal rapide, en moins de 48h, de la trisomie 21 sur

  12. Aberrant lymphatic development in euploid fetuses with increased nuchal translucency including Noonan syndrome.

    NARCIS (Netherlands)

    Mooij, Y.M. de; Akker, N.M. van den; Bekker, M.N.; Bartelings, M.M.; Vugt, J.M.G. van; Gittenberger-de Groot, A.C.

    2011-01-01

    OBJECTIVE: Increased nuchal translucency in the human fetus is associated with aneuploidy, structural malformations and several syndromes such as Noonan syndrome. In 60-70% of the Noonan syndrome cases, a gene mutation can be demonstrated. Previous research showed that aneuploid fetuses with increas

  13. Biodiversity conservation including uncharismatic species

    DEFF Research Database (Denmark)

    Muñoz, Joaquin

    2007-01-01

    (Chapron 2006; Schwartz 2006), and the main threats to biodiversity (including invasive species) (Bawa 2006). I suggest, however, that these articles do not really deal with biodiversity. Rather, they all focus on a few obviously charismatic groups (mammals, birds, some plants, fishes, human culture......). Mammals and birds have traditionally been proposed as umbrella or flagship species (‘‘species that needs such large tracts of habitat that saving it will automatically save many other species’’––Simberloff 1998), to identify areas suitable as nature reserves (Kerr 1997; Sergio et al. 2005)....

  14. Theory including future not excluded

    DEFF Research Database (Denmark)

    Nagao, K.; Nielsen, H.B.

    2013-01-01

    We study a complex action theory (CAT) whose path runs over not only past but also future. We show that, if we regard a matrix element defined in terms of the future state at time T and the past state at time TA as an expectation value in the CAT, then we are allowed to have the Heisenberg equation......, Ehrenfest's theorem, and the conserved probability current density. In addition,we showthat the expectation value at the present time t of a future-included theory for large T - t and large t - T corresponds to that of a future-not-included theory with a proper inner product for large t - T. Hence, the CAT...... with future explicitly present in the formalism and influencing in principle the past is not excluded phenomenologically, because the effects are argued to be very small in the present era. Furthermore, we explicitly derive the Hamiltonian for the future state via a path integral, and confirm that it...

  15. DNA aneuploidy in colorectal adenomas: Role in the adenoma-carcinoma sequence Aneuploidía del ADN en adenomas colónicos: Papel en la secuencia adenoma-carcinoma

    Directory of Open Access Journals (Sweden)

    M. Alcántara Torres

    2005-01-01

    Full Text Available Introduction: aneuploidy has been observed in 6-27% of lesions known to be precursors of colorectal cancer, such as adenomas or ulcerative colitis. It has been suggested that aneuploidy may predispose to malignancy in these cases. However, its role in the adenoma-carcinoma sequence has not been definitely established. The objective of this study was to assess the incidence of aneuploidy in colon adenomas, as well as to study its possible role in the adenoma-carcinoma sequence. Material and methods: the study was performed on a series of 57 large bowel adenomas measuring 10 mm or more, collected from 54 consecutive patients. All specimens were obtained either by endoscopic or by surgical resection. There were 49 adenomas with low-grade dysplasia, two with high-grade dysplasia, two intramucous carcinomas, and four microinvasive carcinomas. A flow cytometric DNA analysis was performed in fresh specimens following Vindelov´s method. Results: aneuploid DNA was detected in five out of 49 low-grade dysplasia adenomas (10%, in all four high-grade dysplasia adenomas or intramucous carcinomas (100%, and in three out of four microinvasive carcinomas (75%. The association between aneuploidy and high-grade dysplasia adenomas, intramucous, or microinvasive carcinoma was statistically significant (p Introducción: en patología benigna de intestino grueso precursora del cáncer colorrectal, como adenomas o colitis ulcerosa, se ha observado aneuploidía en el 6-27% de los casos y se ha sugerido que su presencia predispone al desarrollo de malignidad. Sin embargo, su papel en la secuencia adenoma-carcinoma no se ha demostrado de forma concluyente. El objetivo de nuestro trabajo fue valorar la incidencia de aneuploidía en adenomas colónicos, con y sin signos de malignidad, y estudiar su posible papel en la secuencia adenoma-carcinoma. Material y métodos: el estudio se realizó en una serie de 57 adenomas de intestino grueso, de 10 o más mil

  16. Families classification including multiopposition asteroids

    Science.gov (United States)

    Milani, Andrea; Spoto, Federica; Knežević, Zoran; Novaković, Bojan; Tsirvoulis, Georgios

    2016-01-01

    In this paper we present the results of our new classification of asteroid families, upgraded by using catalog with > 500,000 asteroids. We discuss the outcome of the most recent update of the family list and of their membership. We found enough evidence to perform 9 mergers of the previously independent families. By introducing an improved method of estimation of the expected family growth in the less populous regions (e.g. at high inclination) we were able to reliably decide on rejection of one tiny group as a probable statistical fluke. Thus we reduced our current list to 115 families. We also present newly determined ages for 6 families, including complex 135 and 221, improving also our understanding of the dynamical vs. collisional families relationship. We conclude with some recommendations for the future work and for the family name problem.

  17. Two-Dimensional Differential Gel Electrophoresis to Identify Protein Biomarkers in Amniotic Fluid of Edwards Syndrome (Trisomy 18 Pregnancies.

    Directory of Open Access Journals (Sweden)

    Te-Yao Hsu

    Full Text Available Edwards syndrome (ES is a severe chromosomal abnormality with a prevalence of about 0.8 in 10,000 infants born alive. The aims of this study were to identify candidate proteins associated with ES pregnancies from amniotic fluid supernatant (AFS using proteomics, and to explore the role of biological networks in the pathophysiology of ES.AFS from six second trimester pregnancies with ES fetuses and six normal cases were included in this study. Fluorescence-based two-dimensional difference gel electrophoresis (2D-DIGE and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS were used for comparative proteomic analysis. The identified proteins were further validated by Western blotting and the role of biological networks was analyzed.Twelve protein spots were differentially expressed by more than 1.5-fold in the AFS of the ES pregnancies. MALDI-TOF/MS identified one up-regulated protein: apolipoprotein A1 (ApoA1, and four under-regulated proteins: vitamin D binding protein (VDBP, alpha-1-antitrypsin (A1AT, insulin-like growth factor-binding protein 1 (IGFBP-1, and transthyretin (TTR. Western blot and densitometric analysis of ApoA1, A1AT, IGFBP-1, and TTR confirmed the alteration of these proteins in the amniotic fluid samples. Biological network analysis revealed that the proteins of the ES AFS were involved mainly in lipid and hormone metabolism, immune response, and cardiovascular disease.These five proteins may be involved in the pathogenesis of ES. Further studies are needed to explore.

  18. Brake assembly including torque monitor

    International Nuclear Information System (INIS)

    This patent describes a brake assembly for selectively braking rotation of an input shaft extending from a control rod drive having a longitudinal centerline axis, the shaft being rotatable for selectively inserting and withdrawing a control rod in a nuclear reactor vessel. It comprises a stationary base; an annular bearing mounted to the base; a brake mounted to the bearing; a backing plate mounted to the bearing; a first braking pad fixedly joined to the backing plate; a rotor disc fixedly connected to the input shaft and disposed adjacent to the first pad; a second braking pad disposed adjacent to the rotor disc; and means for selectively clamping the first and second pads against the rotor disc for braking the input shaft; means for torsionally restraining the brake including: a pin extending outwardly from the backing plate toward the base; and a spring extending from the base to the pin and generally perpendicular to the centerline axis; and means for monitoring the angle for monitoring braking torque capability of the brake

  19. De novo trisomy 16p

    Energy Technology Data Exchange (ETDEWEB)

    Juan, J.L.C.; Cigudosa, J.C.; Gomez, A.O. [Univ. of La Laguna, Tenerife, Canary Islands (Spain)] [and others

    1997-01-20

    We report on a patient with psychomotor retardation and a pattern of malformations comprising single umbilical artery, craniofacial anomalies, severe truncal hypotonia, and lower-limb hyporreflexia. G-banding cytogenetics demonstrated a 16p+ chromosome. Parental chromosomes were normal. The use of fluorescent in situ hybridization (FISH) showed that this extra material derived from chromosome 16. High-resolution G-banding demonstrated a duplicated segment on the 16p arm, confirming our suspicion of a de novo tandem duplication; hence, the cytogenetic diagnosis was given as 46,XY,dir dup(16)(p11.2{r_arrow}p12). 9 refs., 3 figs.

  20. Genetics Home Reference: trisomy 18

    Science.gov (United States)

    ... during the formation of reproductive cells (eggs and sperm) or very early in embryonic development. Affected individuals ... random events during the formation of eggs and sperm. An error in cell division called nondisjunction results ...

  1. Genetics Home Reference: trisomy 13

    Science.gov (United States)

    ... during the formation of reproductive cells (eggs and sperm) or very early in fetal development. Affected people ... random events during the formation of eggs and sperm in healthy parents. An error in cell division ...

  2. Utilization of Benchtop Next Generation Sequencing Platforms Ion Torrent PGM and MiSeq in Noninvasive Prenatal Testing for Chromosome 21 Trisomy and Testing of Impact of In Silico and Physical Size Selection on Its Analytical Performance.

    Directory of Open Access Journals (Sweden)

    Gabriel Minarik

    Full Text Available The aims of this study were to test the utility of benchtop NGS platforms for NIPT for trisomy 21 using previously published z score calculation methods and to optimize the sample preparation and data analysis with use of in silico and physical size selection methods.Samples from 130 pregnant women were analyzed by whole genome sequencing on benchtop NGS systems Ion Torrent PGM and MiSeq. The targeted yield of 3 million raw reads on each platform was used for z score calculation. The impact of in silico and physical size selection on analytical performance of the test was studied.Using a z score value of 3 as the cut-off, 98.11%-100% (104-106/106 specificity and 100% (24/24 sensitivity and 99.06%-100% (105-106/106 specificity and 100% (24/24 sensitivity were observed for Ion Torrent PGM and MiSeq, respectively. After in silico based size selection both platforms reached 100% specificity and sensitivity. Following the physical size selection z scores of tested trisomic samples increased significantly--p = 0.0141 and p = 0.025 for Ion Torrent PGM and MiSeq, respectively.Noninvasive prenatal testing for chromosome 21 trisomy with the utilization of benchtop NGS systems led to results equivalent to previously published studies performed on high-to-ultrahigh throughput NGS systems. The in silico size selection led to higher specificity of the test. Physical size selection performed on isolated DNA led to significant increase in z scores. The observed results could represent a basis for increasing of cost effectiveness of the test and thus help with its penetration worldwide.

  3. Detection of fetal cell-free DNA in maternal plasma for Down syndrome, Edward syndrome and Patau syndrome of high risk fetus

    OpenAIRE

    Ke, Wei-Lin; Zhao, Wei-Hua; Wang, Xin-Yu

    2015-01-01

    Objective: The study aimed to validate the efficacy of detection of fetal cell-free DNA in maternal plasma of trisomy 21, 18 and 13 in a clinical setting. Methods: A total of 2340 women at high risk for Down syndrome based on maternal age, prenatal history or a positive sesum or sonographic screening test were offered prenatal noninvasive aneuploidy test. According to the prenatal noninvasive aneuploidy test, the pregnant women at high risk were offered amniocentesis karyotype analysis and th...

  4. Morphological Integration of Soft-Tissue Facial Morphology in Down Syndrome and Siblings

    OpenAIRE

    Starbuck, John; Reeves, Roger H.; Richtsmeier, Joan

    2011-01-01

    Down syndrome (DS), resulting from trisomy of chromosome 21, is the most common live-born human aneuploidy. The phenotypic expression of trisomy 21 produces variable, though characteristic, facial morphology. Although certain facial features have been documented quantitatively and qualitatively as characteristic of DS (e.g., epicanthic folds, macroglossia, and hypertelorism), all of these traits occur in other craniofacial conditions with an underlying genetic cause. We hypothesize that the t...

  5. Down syndrome child with 48,XXY,+21 karyotype

    Directory of Open Access Journals (Sweden)

    Cyrus Cyril

    2005-01-01

    Full Text Available Cytogenetic analysis in 60 clinically suspected cases of Down syndrome and their parents was carried out using conventional Giemsa-trypsin-banding technique. Fifty-five individuals (91% exhibited a free trisomy 21. Robertsonian translocations were seen in three cases and two cases exhibited a normal karyotype. A four-month-old child, the second-born of non-consanguineous parents, possessed an extra X chromosome in addition to trisomy 21. The proband′s parents and his brother showed a normal karyotype. The phenotypic characteristics of this child have been discussed in the light of the published reports on double aneuploidies of XXY and trisomy 21.

  6. International, collaborative assessment of limitations of chromosome-specific probes (CSP) and fluorescent in situ hybridization (FISH): Analysis of expected detections in 73,000 prenatal cases

    Energy Technology Data Exchange (ETDEWEB)

    Evans, M.I.; Henry, G.P.; Miller, W.A. [Wayne State Univ., Detroit, MI (United States)] [and others

    1994-09-01

    FISH and CSP have been proposed to reduce karyotyping need. The purpose of this study was to assess the potential efficacy of CSP-FISH using currently available probes (13, 18, 21, X, & Y) in large, prenatal diagnostic centers. Results (1990-1993) from 7 centers in 4 countries were divided by those expected to be detectable by currently available probes, and those which would be missed assuming 10% probe efficacy. 72,994 karyotypes included 699 trisomy 21`s, 352 trisomy 18`s, 136 trisomy 13`s, 358 sex chromosome aneuploidies, 70 triploidies, and 855 others (translocations, inversions, deletions, markers). Of 2,613 abnormalities, 1,745 would be detectable (66.8%). [Detroit 55.7%, Stockholm 68.3%, Boston 52.6%, Denver 61.3%, Muenster 77.0%, London 84.5%, Philadelphia 69.4%]. Centers with high proportions of referrals for ultrasound anomalies had the highest CSP-FISH positives secondary to increased T 18 & 13. We conclude: (1) 73,000 karyotypes show relatively consistent incidences of the common trisomies, sex chromosome abnormalities, and other chromosome abnormalities among the centers. (2) The proportion expected detectable by FISH-CSP technology varies from 52.6% to 84.5%, averaging 66.8%. (3) 1/3 of the karyotypic abnormalities would be missed, and therefore, replacement of complete karyotyping with FISH would have unacceptably high false-negative rates for routine evaluation. (4) FISH-CSP, while useful when positive for anomalies, is not sufficient when negative to obviate the need for a complete karyotype.

  7. Static, Lightweight Includes Resolution for PHP

    NARCIS (Netherlands)

    Hills, M.A.; Klint, P.; Vinju, J.J.

    2014-01-01

    Dynamic languages include a number of features that are challenging to model properly in static analysis tools. In PHP, one of these features is the include expression, where an arbitrary expression provides the path of the file to include at runtime. In this paper we present two complementary analy

  8. Article Including Environmental Barrier Coating System

    Science.gov (United States)

    Lee, Kang N. (Inventor)

    2015-01-01

    An enhanced environmental barrier coating for a silicon containing substrate. The enhanced barrier coating may include a bond coat doped with at least one of an alkali metal oxide and an alkali earth metal oxide. The enhanced barrier coating may include a composite mullite bond coat including BSAS and another distinct second phase oxide applied over said surface.

  9. The consequences of implementing non-invasive prenatal testing in Dutch national health care: a cost-effectiveness analysis

    NARCIS (Netherlands)

    Beulen, L.; Grutters, J.P.C.; Faas, B.H.W.; Feenstra, I.; Vugt, J.M.G. van; Bekker, M.N.

    2014-01-01

    OBJECTIVE: Non-invasive prenatal testing (NIPT) using cell-free fetal DNA in maternal plasma has been developed for the detection of fetal aneuploidy. Clinical trials have shown high sensitivity and specificity for trisomy 21 (T21) in both high-risk and average-risk populations. Although its great p

  10. Composite Pressure Vessel Including Crack Arresting Barrier

    Science.gov (United States)

    DeLay, Thomas K. (Inventor)

    2013-01-01

    A pressure vessel includes a ported fitting having an annular flange formed on an end thereof and a tank that envelopes the annular flange. A crack arresting barrier is bonded to and forming a lining of the tank within the outer surface thereof. The crack arresting barrier includes a cured resin having a post-curing ductility rating of at least approximately 60% through the cured resin, and further includes randomly-oriented fibers positioned in and throughout the cured resin.

  11. 28 CFR 20.32 - Includable offenses.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Includable offenses. 20.32 Section 20.32 Judicial Administration DEPARTMENT OF JUSTICE CRIMINAL JUSTICE INFORMATION SYSTEMS Federal Systems and Exchange of Criminal History Record Information § 20.32 Includable offenses. (a) Criminal history...

  12. Haemophilus influenzae Disease (Including Hib) Symptoms

    Science.gov (United States)

    ... is considered invasive. Symptoms of pneumonia usually include: Fever and chills Cough Shortness of breath or difficulty breathing Sweating ... the blood. It can cause symptoms such as: Fever and chills Excessive tiredness Pain in the belly Nausea with ...

  13. What Does Long-Term Care Include?

    Medline Plus

    Full Text Available Video: "What Does Long-Term Care Include?" Long-term care involves a variety of services designed to meet a person's health or personal care needs during a short or long period of ...

  14. Births and deaths including fetal deaths

    Data.gov (United States)

    U.S. Department of Health & Human Services — Access to a variety of United States birth and death files including fetal deaths: Birth Files, 1968-2009; 1995-2005; Fetal death file, 1982-2005; Mortality files,...

  15. Include Passive Solar in Your Renovations.

    Science.gov (United States)

    Bender, Gerald F.; Probasco, Jack F.

    1981-01-01

    A checklist covers potential energy saving modifications in a building scheduled for renovation, and includes suggestions for room utilization, landscaping, and building envelope, solar control, and active system modifications. (Author)

  16. Including Indigenous Minorities in Decision-Making

    DEFF Research Database (Denmark)

    Pristed Nielsen, Helene

    Based on theories of public sphere participation and deliberative democracy, this book presents empirical results from a study of experiences with including Aboriginal and Maori groups in political decision-making in respectively Western Australia and New Zealand......Based on theories of public sphere participation and deliberative democracy, this book presents empirical results from a study of experiences with including Aboriginal and Maori groups in political decision-making in respectively Western Australia and New Zealand...

  17. Including excitons in semiconductor solar cell modelling

    OpenAIRE

    Burgelman, Marc; Minnaert, Ben

    2005-01-01

    Excitons are marginally important in classical semiconductor device physics, and their treatment is not included in standard solar cell modelling. However, in organic semiconductors and solar cells, the role of excitons is essential, as the primary effect of light absorption is exciton generation, and free electrons and holes are created by exciton dissociation. First steps to include excitons in solar cell modelling were presented by Green 1996 and Zhang 1998. Their model was restricted to a...

  18. Gas storage materials, including hydrogen storage materials

    Science.gov (United States)

    Mohtadi, Rana F; Wicks, George G; Heung, Leung K; Nakamura, Kenji

    2013-02-19

    A material for the storage and release of gases comprises a plurality of hollow elements, each hollow element comprising a porous wall enclosing an interior cavity, the interior cavity including structures of a solid-state storage material. In particular examples, the storage material is a hydrogen storage material such as a solid state hydride. An improved method for forming such materials includes the solution diffusion of a storage material solution through a porous wall of a hollow element into an interior cavity.

  19. Relevance to Aging and Dementia

    Directory of Open Access Journals (Sweden)

    Pinar E. Coskun

    2012-01-01

    Full Text Available Genome-wide gene deregulation and oxidative stress appear to be critical factors determining the high variability of phenotypes in Down’s syndrome (DS. Even though individuals with trisomy 21 exhibit a higher survival rate compared to other aneuploidies, most of them die in utero or early during postnatal life. While the survivors are currently predicted to live past 60 years, they suffer higher incidence of age-related conditions including Alzheimer’s disease (AD. This paper is centered on the mechanisms by which mitochondrial factors and oxidative stress may orchestrate an adaptive response directed to maintain basic cellular functions and survival in DS. In this context, the timing of therapeutic interventions should be carefully considered for the successful treatment of chronic disorders in the DS population.

  20. A simple screening method for detection of Klinefelter syndrome and other X-chromosome aneuploidies based on copy number of the androgen receptor gene

    DEFF Research Database (Denmark)

    Ottesen, A M; Garn, I D; Aksglaede, L; Juul, A; Rajpert-De Meyts, E

    2007-01-01

    copy number assessment of the androgen receptor (AR) gene, located to Xq11.2-q12. We analysed samples from 50 individuals, including a healthy male and female controls and patients with Klinefelter syndrome (47,XXY; 48,XXXY) (n = 28), mosaicisms (46,XX/47,XXY/48XXYY; 45,X/46,XY) (n = 3), other sex...... chromosome abnormalities (46,XX males; 47,XYY)(n = 4) and normal karyotypes (46,XY) (n = 13). The reference range for the AR-copy number was established as 0.8-1.2 for one copy and 1.7-2.3 for two copies. The qPCR results were within the reference range in 17/18 samples (94%) or 30/31 (97%) samples with one...... or two copies of the AR gene, respectively. None of the Klinefelter patients were misdiagnosed as having a karyotype with only one X-chromosome, and in none of the 46,XY males were two copies demonstrated. We systematically compared qPCR results with those obtained with another PCR-based method, the...

  1. The Social Behavioral Phenotype in Boys and Girls with an Extra X Chromosome (Klinefelter Syndrome and Trisomy X) : A Comparison with Autism Spectrum Disorder

    NARCIS (Netherlands)

    van Rijn, Sophie; Stockmann, Lex; Borghgraef, Martine; Bruining, Hilgo; van Ravenswaaij-Arts, Conny; Govaerts, Lutgarde; Hansson, Kerstin; Swaab, Hanna

    2014-01-01

    The present study aimed to gain more insight in the social behavioral phenotype, and related autistic symptomatology, of children with an extra X chromosome in comparison to children with ASD. Participants included 60 children with an extra X chromosome (34 boys with Klinefelter syndrome and 26 girl

  2. Transmission line including support means with barriers

    Science.gov (United States)

    Cookson, Alan H.

    1982-01-01

    A gas insulated transmission line includes an elongated outer sheath, a plurality of inner conductors disposed within and extending along the outer sheath, and an insulating gas which electrically insulates the inner conductors from the outer sheath. A support insulator insulatably supports the inner conductors within the outer sheath, with the support insulator comprising a main body portion including a plurality of legs extending to the outer sheath, and barrier portions which extend between the legs. The barrier portions have openings therein adjacent the main body portion through which the inner conductors extend.

  3. Electric Power Monthly, August 1990. [Glossary included

    Energy Technology Data Exchange (ETDEWEB)

    1990-11-29

    The Electric Power Monthly (EPM) presents monthly summaries of electric utility statistics at the national, Census division, and State level. The purpose of this publication is to provide energy decisionmakers with accurate and timely information that may be used in forming various perspectives on electric issues that lie ahead. Data includes generation by energy source (coal, oil, gas, hydroelectric, and nuclear); generation by region; consumption of fossil fuels for power generation; sales of electric power, cost data; and unusual occurrences. A glossary is included.

  4. 42 CFR 409.10 - Included services.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Included services. 409.10 Section 409.10 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE PROGRAM HOSPITAL INSURANCE BENEFITS Inpatient Hospital Services and Inpatient Critical Access Hospital...

  5. West syndrome associated with a novel chromosomal anomaly; partial trisomy 8P together with partial monosomy 9P, resulting from a familial unbalanced reciprocal translocation

    OpenAIRE

    Ilknur Erol; Semra Saygi; Senay Demir; Fusun Alehan; Feride Iffet Sahin

    2015-01-01

    West syndrome is classified according to the underlying etiology into an acquired West syndrome, a congenital/developmental West syndrome, and West syndrome of unknown etiology. Causes of a congenital/developmental West syndrome are extensive and include chromosomal anomalies. We report on a patient carrying a derivative chromosome originating from the reciprocal unbalanced translocation t (8;9) (p11.2;p22) and presenting with macrocephaly, West syndrome, severe mental motor retardation and h...

  6. 辅助生殖技术治疗后孕早期自然流产的绒毛细胞染色体分析%Chromosomal Analysis in Spontaneous Abortion during the First Trimester after Assisted Reproduction Technique Treatment

    Institute of Scientific and Technical Information of China (English)

    李跃萍; 徐雯; 黎明红; 麦扬青; 陈竞茜; 闫庆峰

    2011-01-01

    Objective To know about chromosome abnormalities in spontaneous abortion during the first trimester after assisted reproduction technique treatment and to provide some data for eugenics. Methods A retrospective analysis was performed on 41 clinical spontaneous abortion cases during the first trimester following ART, which including in vitro fertilization-embryo transfer (IVF-ET) and intracytoplasmic sperm injection (ICSI) and frozen embryo transfer (F-ET) and intrauterine insemination (IUI). Cytogenetic analysis of the chorionic villi by cell culture and standard G-banding cytogenetic techniques was performed. Results Successful analysis was conducted in 30 specimens. Fifteen of 30 specimens had a chromosomal abnormality,accounting for 50%. The majorities were numerical abnormalities such as monosomy X (one case). Trisomies for chromosomes 11 cases, including 18 trisomies in one case, 16 trisomies in three cases, 15 trisomies in two case, 4 trisomies in one cases, 9 trisomies in one case, 2 trisomies in one case, mosaic trisomy 21 trisomies in two cases, and polyploidin one case were observed. 46, XX/47, XX, +mar karyotype was observed in one case. Conclusions ART abortion is closely related with embryo chromosome abnormalities. Aneuploidy is the major factor affecting embryonic development in spontaneous abortions during the first trimester after ART.%目的 了解辅助生殖技术(ART)治疗后孕早期自然流产的绒毛细胞染色体的异常情况,为优生优育工作作指导.方法 选择行体外受精-胚胎移植(IVF-ET)、单精子卵胞浆内显微注射( ICSI)、冻融胚胎移植(F-ET)及宫腔内人工授精(IUI)治疗后的自然流产绒毛标本41例,进行绒毛细胞培养及G显带,分析染色体核型.结果 41例标本中有30例培养成功,绒毛染色体异常15例,占50%.多数为数目异常,其中X单体1例,染色体三体11例(包括18三体1例,16三体3例,15三体2例,4号三体1例,9号三体1例,2号三体1

  7. Maternal Plasma DNA and RNA Sequencing for Prenatal Testing.

    Science.gov (United States)

    Tamminga, Saskia; van Maarle, Merel; Henneman, Lidewij; Oudejans, Cees B M; Cornel, Martina C; Sistermans, Erik A

    2016-01-01

    Cell-free DNA (cfDNA) testing has recently become indispensable in diagnostic testing and screening. In the prenatal setting, this type of testing is often called noninvasive prenatal testing (NIPT). With a number of techniques, using either next-generation sequencing or single nucleotide polymorphism-based approaches, fetal cfDNA in maternal plasma can be analyzed to screen for rhesus D genotype, common chromosomal aneuploidies, and increasingly for testing other conditions, including monogenic disorders. With regard to screening for common aneuploidies, challenges arise when implementing NIPT in current prenatal settings. Depending on the method used (targeted or nontargeted), chromosomal anomalies other than trisomy 21, 18, or 13 can be detected, either of fetal or maternal origin, also referred to as unsolicited or incidental findings. For various biological reasons, there is a small chance of having either a false-positive or false-negative NIPT result, or no result, also referred to as a "no-call." Both pre- and posttest counseling for NIPT should include discussing potential discrepancies. Since NIPT remains a screening test, a positive NIPT result should be confirmed by invasive diagnostic testing (either by chorionic villus biopsy or by amniocentesis). As the scope of NIPT is widening, professional guidelines need to discuss the ethics of what to offer and how to offer. In this review, we discuss the current biochemical, clinical, and ethical challenges of cfDNA testing in the prenatal setting and its future perspectives including novel applications that target RNA instead of DNA. PMID:27117661

  8. Photoactive devices including porphyrinoids with coordinating additives

    Energy Technology Data Exchange (ETDEWEB)

    Forrest, Stephen R; Zimmerman, Jeramy; Yu, Eric K; Thompson, Mark E; Trinh, Cong; Whited, Matthew; Diev, Vlacheslav

    2015-05-12

    Coordinating additives are included in porphyrinoid-based materials to promote intermolecular organization and improve one or more photoelectric characteristics of the materials. The coordinating additives are selected from fullerene compounds and organic compounds having free electron pairs. Combinations of different coordinating additives can be used to tailor the characteristic properties of such porphyrinoid-based materials, including porphyrin oligomers. Bidentate ligands are one type of coordinating additive that can form coordination bonds with a central metal ion of two different porphyrinoid compounds to promote porphyrinoid alignment and/or pi-stacking. The coordinating additives can shift the absorption spectrum of a photoactive material toward higher wavelengths, increase the external quantum efficiency of the material, or both.

  9. Including knowledge creation & enabling in risk management

    OpenAIRE

    Hop, Eirik

    2015-01-01

    As a contribution to Statoil Technical Efficiency Programme (STEP), has the thesis looked at how to improve the risk management process in Statoil ASA. Through theoretical research was the primary research question created: “How can knowledge creation & enabling improve our understanding of risk management?” To create a theoretical foundation, the thesis looked at principles, methods, and models for the adequate assessment and management of risk. This includes a new perspective on ri...

  10. Rotor assembly including superconducting magnetic coil

    Science.gov (United States)

    Snitchler, Gregory L.; Gamble, Bruce B.; Voccio, John P.

    2003-01-01

    Superconducting coils and methods of manufacture include a superconductor tape wound concentrically about and disposed along an axis of the coil to define an opening having a dimension which gradually decreases, in the direction along the axis, from a first end to a second end of the coil. Each turn of the superconductor tape has a broad surface maintained substantially parallel to the axis of the coil.

  11. Including heavy flavour production in PDF fits

    OpenAIRE

    A.M. Cooper-Sarkar

    2007-01-01

    AT HERA heavy quarks may contribute up to 30% of the structure function $F_2$. The introduction of heavy quarks requires an extension of the DGLAP formalism. The effect of using different heavy flavour number schemes, and different approaches to the running of $\\alpha_s$, are compared using the ZEUS PDF fit formalism. The potential of including charm data in the fit is explored, using $D^*$ double differential cross-sections rather than the inclusive quantity $F_2^{c\\bar{c}}$.

  12. Model for safety reports including descriptive examples

    International Nuclear Information System (INIS)

    Several safety reports will be produced in the process of planning and constructing the system for disposal of high-level radioactive waste in Sweden. The present report gives a model, with detailed examples, of how these reports should be organized and what steps they should include. In the near future safety reports will deal with the encapsulation plant and the repository. Later reports will treat operation of the handling systems and the repository

  13. Electric power monthly, September 1990. [Glossary included

    Energy Technology Data Exchange (ETDEWEB)

    1990-12-17

    The purpose of this report is to provide energy decision makers with accurate and timely information that may be used in forming various perspectives on electric issues. The power plants considered include coal, petroleum, natural gas, hydroelectric, and nuclear power plants. Data are presented for power generation, fuel consumption, fuel receipts and cost, sales of electricity, and unusual occurrences at power plants. Data are compared at the national, Census division, and state levels. 4 figs., 52 tabs. (CK)

  14. The surgery of peripheral nerves (including tumors)

    DEFF Research Database (Denmark)

    Fugleholm, Kåre

    2013-01-01

    Surgical pathology of the peripheral nervous system includes traumatic injury, entrapment syndromes, and tumors. The recent significant advances in the understanding of the pathophysiology and cellular biology of peripheral nerve degeneration and regeneration has yet to be translated into improved...... nervous system response to injury are prerequisite to obtain the best possible outcome. Surgery continues to be the primary treatment modality for peripheral nerve tumors and advances in adjuvant oncological treatment has improved outcome after malignant peripheral nerve tumors. The present chapter...

  15. West syndrome associated with a novel chromosomal anomaly; partial trisomy 8P together with partial monosomy 9P, resulting from a familial unbalanced reciprocal translocation

    Directory of Open Access Journals (Sweden)

    Ilknur Erol

    2015-01-01

    Full Text Available West syndrome is classified according to the underlying etiology into an acquired West syndrome, a congenital/developmental West syndrome, and West syndrome of unknown etiology. Causes of a congenital/developmental West syndrome are extensive and include chromosomal anomalies. We report on a patient carrying a derivative chromosome originating from the reciprocal unbalanced translocation t (8;9 (p11.2;p22 and presenting with macrocephaly, West syndrome, severe mental motor retardation and hypotonia. As far as we know, this is a new chromosomal anomaly associated with West syndrome.

  16. A kicked quantum system including the continuum

    International Nuclear Information System (INIS)

    The behaviour of a quantum particle in a separable one-term potential with three-dimensional form factor is investigated under the influence of an external force which alters the potential strength periodically or quasiperiodically. The unperturbed system possesses one bound state and a continuum of scattering states which has treated almost analytically. First numerical results, fully including the emission channel, indicate, for certain parameter combinations with commensurate or incommensurate frequency ratios, either a regular or an irregular dynamical behaviour of the system. 17 refs.; 3 figs

  17. Aerosol simulation including chemical and nuclear reactions

    Energy Technology Data Exchange (ETDEWEB)

    Marwil, E.S.; Lemmon, E.C.

    1985-01-01

    The numerical simulation of aerosol transport, including the effects of chemical and nuclear reactions presents a challenging dynamic accounting problem. Particles of different sizes agglomerate and settle out due to various mechanisms, such as diffusion, diffusiophoresis, thermophoresis, gravitational settling, turbulent acceleration, and centrifugal acceleration. Particles also change size, due to the condensation and evaporation of materials on the particle. Heterogeneous chemical reactions occur at the interface between a particle and the suspending medium, or a surface and the gas in the aerosol. Homogeneous chemical reactions occur within the aersol suspending medium, within a particle, and on a surface. These reactions may include a phase change. Nuclear reactions occur in all locations. These spontaneous transmutations from one element form to another occur at greatly varying rates and may result in phase or chemical changes which complicate the accounting process. This paper presents an approach for inclusion of these effects on the transport of aerosols. The accounting system is very complex and results in a large set of stiff ordinary differential equations (ODEs). The techniques for numerical solution of these ODEs require special attention to achieve their solution in an efficient and affordable manner. 4 refs.

  18. Is routine karyotyping required in prenatal samples with a molecular or metabolic referral?

    Directory of Open Access Journals (Sweden)

    Kooper Angelique JA

    2012-01-01

    Full Text Available Abstract As a routine, karyotyping of invasive prenatal samples is performed as an adjunct to referrals for DNA mutation detection and metabolic testing. We performed a retrospective study on 500 samples to assess the diagnostic value of this procedure. These samples included 454 (90.8% chorionic villus (CV and 46 (9.2% amniocenteses specimens. For CV samples karyotyping was based on analyses of both short-term culture (STC and long-term culture (LTC cells. Overall, 19 (3.8% abnormal karyotypes were denoted: four with a common aneuploidy (trisomy 21, 18 and 13, two with a sex chromosomal aneuploidy (Klinefelter syndrome, one with a sex chromosome mosaicism and twelve with various autosome mosaicisms. In four cases a second invasive test was performed because of an abnormal finding in the STC. Taken together, we conclude that STC and LTC karyotyping has resulted in a diagnostic yield of 19 (3.8% abnormal cases, including 12 cases (2.4% with an uncertain significance. From a diagnostic point of view, it is desirable to limit uncertain test results as secondary test findings. Therefore, we recommend a more targeted assay, such as e.g. QF-PCR, as a replacement of the STC and to provide parents the autonomy to choose between karyotyping and QF-PCR.

  19. Non-Invasive Prenatal Testing Using Cell Free DNA in Maternal Plasma: Recent Developments and Future Prospects

    Directory of Open Access Journals (Sweden)

    Peter Benn

    2014-05-01

    Full Text Available Recent advances in molecular genetic technologies have facilitated non-invasive prenatal testing (NIPT through the analysis of cell-free fetal DNA in maternal plasma. NIPT can be used to identify monogenic disorders including the identification of autosomal recessive disorders where the maternally inherited mutation needs to be identified in the presence of an excess of maternal DNA that contains the same mutation. In the future, simultaneous screening for multiple monogenic disorders is anticipated. Several NIPT methods have been developed to screen for trisomy. These have been shown to be effective for fetal trisomy 21, 18 and 13. Although the testing has been extended to sex chromosome aneuploidy, robust estimates of the efficacy are not yet available and maternal mosaicism for gain or loss of an X-chromosome needs to be considered. Using methods based on the analysis of single nucleotide polymorphisms, diandric triploidy can be identified. NIPT is being developed to identify a number of microdeletion syndromes including α-globin gene deletion. NIPT is a profoundly important development in prenatal care that is substantially advancing the individual patient and public health benefits achieved through conventional prenatal screening and diagnosis.

  20. ACCREDITATION FOR TECHNICAL ABILITIES INCLUDING COMPUTER SKILLS

    Directory of Open Access Journals (Sweden)

    Halit Hami OZ

    2013-01-01

    Full Text Available Sector Skills are defined by state-sponsored, employer-led organizations that cover specific economic sectors in the European Union and other countries in the world to reduce skills gaps and shortages, improve productivity, boost the skills of their sector workforces and improve learning supply. The accreditation and registration systems used by professional bodies raise the profile of the profession. In many countries including the European Union, professional associations are beginning to accept practice-based accreditation, generally as an alternative to their mainstream systems. Besides studying the certain agencies in the European Union for assessing/accreditating practical abilities , Accreditation for practical abilities of Information Communication Technology and Business Management/Language domains developed by Accreditation Council for Practical abilities are also studied in detail as an example to establish a similar agency in Turkey.

  1. Including electronic effects in damage cascade simulations

    International Nuclear Information System (INIS)

    A method for including the effects of electronic losses and electron-phonon coupling in radiation damage simulations has been developed and implemented for 10 keV cascades in Fe. The MD simulations are coupled to a continuum model for the electronic energy and energy lost by the atoms, due to electronic friction and electron-phonon coupling, is gained by electronic system. Electronic energy transport is described by the heat diffusion equation and energy is returned to the lattice via a stochastic force. Thus the temperature of the atomic system is controlled by a Langevin thermostat at the local electronic temperature, which varies with time and space. The results of simulations with this inhomogeneous thermostat are compared with those of homogeneous (constant temperature) thermostat simulations for a range of electron-phonon coupling strengths. The residual defect concentration was found to have a non-monotonic variation with coupling strength.

  2. Input parameters and scenarios, including economic inputs

    DEFF Research Database (Denmark)

    Boklund, Anette; Hisham Beshara Halasa, Tariq

    2012-01-01

    place, a receiving herd needed to be found. The distance, in which the receiving herd should be found, was calculated from movement data for animals and from data from trucks and abattoirs for movements to slaughter and milk tankers. For persons visiting herds, we used a combination of expert opinions......Geographical locations of the farms are the core in these models. We used geographical data, number of animals and specification of herd types for the 50,853 herds in the Danish Husbandry Register (CHR) in 2007. For each herd, the daily probability of moving animals, to another herd or to the......, disease was simulated to spread via direct contacts (movements of animals), indirect contacts (trucks and persons) and local spread (mice, birds, airborne spread in limited distances). Furthermore, in some scenarios airborne spread was included. For all contact types, when a contact was simulated to take...

  3. Critical point anomalies include expansion shock waves

    Energy Technology Data Exchange (ETDEWEB)

    Nannan, N. R., E-mail: ryan.nannan@uvs.edu [Mechanical Engineering Discipline, Anton de Kom University of Suriname, Leysweg 86, PO Box 9212, Paramaribo, Suriname and Process and Energy Department, Delft University of Technology, Leeghwaterstraat 44, 2628 CA Delft (Netherlands); Guardone, A., E-mail: alberto.guardone@polimi.it [Department of Aerospace Science and Technology, Politecnico di Milano, Via La Masa 34, 20156 Milano (Italy); Colonna, P., E-mail: p.colonna@tudelft.nl [Propulsion and Power, Delft University of Technology, Kluyverweg 1, 2629 HS Delft (Netherlands)

    2014-02-15

    From first-principle fluid dynamics, complemented by a rigorous state equation accounting for critical anomalies, we discovered that expansion shock waves may occur in the vicinity of the liquid-vapor critical point in the two-phase region. Due to universality of near-critical thermodynamics, the result is valid for any common pure fluid in which molecular interactions are only short-range, namely, for so-called 3-dimensional Ising-like systems, and under the assumption of thermodynamic equilibrium. In addition to rarefaction shock waves, diverse non-classical effects are admissible, including composite compressive shock-fan-shock waves, due to the change of sign of the fundamental derivative of gasdynamics.

  4. Critical point anomalies include expansion shock waves

    International Nuclear Information System (INIS)

    From first-principle fluid dynamics, complemented by a rigorous state equation accounting for critical anomalies, we discovered that expansion shock waves may occur in the vicinity of the liquid-vapor critical point in the two-phase region. Due to universality of near-critical thermodynamics, the result is valid for any common pure fluid in which molecular interactions are only short-range, namely, for so-called 3-dimensional Ising-like systems, and under the assumption of thermodynamic equilibrium. In addition to rarefaction shock waves, diverse non-classical effects are admissible, including composite compressive shock-fan-shock waves, due to the change of sign of the fundamental derivative of gasdynamics

  5. AMS at the ANU including biomedical applications

    Energy Technology Data Exchange (ETDEWEB)

    Fifield, L.K.; Allan, G.L.; Cresswell, R.G.; Ophel, T.R. [Australian National Univ., Canberra, ACT (Australia); King, S.J.; Day, J.P. [Manchester Univ. (United Kingdom). Dept. of Chemistry

    1993-12-31

    An extensive accelerator mass spectrometry program has been conducted on the 14UD accelerator at the Australian National University since 1986. In the two years since the previous conference, the research program has expanded significantly to include biomedical applications of {sup 26}Al and studies of landform evolution using isotopes produced in situ in surface rocks by cosmic ray bombardment. The system is now used for the measurement of {sup 10}Be, {sup 14}C, {sup 26}Al, {sup 36}Cl, {sup 59}Ni and {sup 129}I, and research is being undertaken in hydrology, environmental geochemistry, archaeology and biomedicine. On the technical side, a new test system has permitted the successful off-line development of a high-intensity ion source. A new injection line to the 14UD has been established and the new source is now in position and providing beams to the accelerator. 4 refs.

  6. CERN Technical Training: LABVIEW courses include RADE

    CERN Multimedia

    HR Department

    2009-01-01

    The contents of the "LabView Basic I" and "LabView Intermediate II" courses have recently been changed to include, respectively, an introduction to and expert training in the Rapid Application Development Environment (RADE). RADE is a LabView-based application developed at CERN to integrate LabView in the accelerator and experiment control infrastructure. It is a suitable solution to developing expert tools, machine development analysis and independent test facilities. The course names have also been changed to "LabVIEW Basics I with RADE Introduction" and "LabVIEW Intermediate II with Advanced RADE Application". " LabVIEW Basics I with RADE Introduction" is designed for: Users preparing to develop applications using LabVIEW, or NI Developer Suite; users and technical managers evaluating LabVIEW or NI Developer Suite in purchasing decisions; users pursuing the Certified LabVIEW Developer certification. The course prepares participants to develop test and measurement, da...

  7. CERN Technical Training: LABVIEW courses include RADE

    CERN Multimedia

    HR Department

    2009-01-01

    The contents of the "LabView Basic I" and "LabView Intermediate II" courses have recently been changed to include, respectively, an introduction to and expert training in the Rapid Application Development Environment (RADE). RADE is a LabView-based application developed at CERN to integrate LabView in the accelerator and experiment control infrastructure. It is a suitable solution to developing expert tools, machine development analysis and independent test facilities. The course names have also been changed to "LabVIEW Basics I with RADE Introduction" and "LabVIEW Intermediate II with Advanced RADE Application". " LabVIEW Basics I with RADE Introduction" is designed for: Users preparing to develop applications using LabVIEW, or NI Developer Suite; users and technical managers evaluating LabVIEW or NI Developer Suite in purchasing decisions; users pursuing the Certified LabVIEW Developer certification. The course pr...

  8. CLIC expands to include the Southern Hemisphere

    CERN Multimedia

    Roberto Cantoni

    2010-01-01

    Australia has recently joined the CLIC collaboration: the enlargement will bring new expertise and resources to the project, and is especially welcome in the wake of CERN budget redistributions following the recent adoption of the Medium Term Plan.   The countries involved in CLIC collaboration With the signing of a Memorandum of Understanding on 26 August 2010, the ACAS network (Australian Collaboration for Accelerator Science) became the 40th member of in the multilateral CLIC collaboration making Australia the 22nd country to join the collaboration. “The new MoU was signed by the ACAS network, which includes the Australian Synchrotron and the University of Melbourne”, explains Jean-Pierre Delahaye, CLIC Study Leader. “Thanks to their expertise, the Australian institutes will contribute greatly to the CLIC damping rings and the two-beam test modules." Institutes from any country wishing to join the CLIC collaboration are invited to assume responsibility o...

  9. CERN Technical Training: LABVIEW courses include RADE

    CERN Multimedia

    HR Department

    2009-01-01

    The contents of "LabView Basic I" and "LabView Intermediate II" trainings have been recently changed to include, respectively, an introduction and an expert training on the Rapid Application Development Environment (RADE). RADE is a LabView-based application developed at CERN to integrate LabView in the accelerator and experiment control infrastructure. It is a suitable solution to develop expert tools, machine development analysis and independent test facilities. The course names have also been changed to "LabVIEW Basics I with RADE Introduction" and "LabVIEW Intermediate II with Advanced RADE Application". " LabVIEW Basics I with RADE Introduction" is designed for: Users preparing to develop applications using LabVIEW, or NI Developer Suite; users and technical managers evaluating LabVIEW or NI Developer Suite in purchasing decisions; users pursuing the Certified LabVIEW Developer certification. The course prepare...

  10. The maternal age-related first trimester risks for trisomy 21, 18 and 13 based on Danish first trimester data from 2005 to 2014

    DEFF Research Database (Denmark)

    Hartwig, Tanja Schlaikjaer; Sørensen, Steen; Jørgensen, Finn Stener

    2016-01-01

    number of included women was 605,853. The total number of T21 cases was 1564, T18 cases was 401 and T13 cases was 157. The overall first trimester prevalence per 10,000 pregnancies was 25.8 for T21, 6.6 for T18 and 2.6 for T13. Boltzmann sigmoidal model (Y = Bottom + (top-bottom / (1-exp (V50-X......OBJECTIVES: Most currently used age-related risks of T21, T18 and T13 are based on estimates of the live-birth prevalence, and describe an exponential increase of risk by increased maternal age. We investigated the first trimester prevalence of T21, T18 and T13 in a large population of Danish women....... METHODS: From the Danish Cytogenetic Central Registry we got the information of all pre- and postnatally diagnosed fetuses with T21, T18 or T13 between 2005 and 2014 in Denmark. Information on the total number of births and maternal age at birth were gathered from StatBank Denmark. RESULTS: The total...

  11. Mapping Breakpoints of Complex Chromosome Rearrangements Involving a Partial Trisomy 15q23.1-q26.2 Revealed by Next Generation Sequencing and Conventional Techniques

    Science.gov (United States)

    Han, Liangrong; Jing, Xin; Liu, Hailiang; Yang, Chuanchun; Zhang, Fengting; Hu, Yue; Yue, Hongni; Ning, Ying

    2016-01-01

    Complex chromosome rearrangements (CCRs), which are rather rare in the whole population, may be associated with aberrant phenotypes. Next-generation sequencing (NGS) and conventional techniques, could be used to reveal specific CCRs for better genetic counseling. We report the CCRs of a girl and her mother, which were identified using a combination of NGS and conventional techniques including G-banding, fluorescence in situ hybridization (FISH) and PCR. The girl demonstrated CCRs involving chromosomes 3 and 8, while the CCRs of her mother involved chromosomes 3, 5, 8, 11 and 15. HumanCytoSNP-12 Chip analysis identified a 35.4 Mb duplication on chromosome 15q21.3-q26.2 in the proband and a 1.6 Mb microdeletion at chromosome 15q21.3 in her mother. The proband inherited the rearranged chromosomes 3 and 8 from her mother, and the duplicated region on chromosome 15 of the proband was inherited from the mother. Approximately one hundred genes were identified in the 15q21.3-q26.2 duplicated region of the proband. In particular, TPM1, SMAD6, SMAD3, and HCN4 may be associated with her heart defects, and HEXA, KIF7, and IDH2 are responsible for her developmental and mental retardation. In addition, we suggest that a microdeletion on the 15q21.3 region of the mother, which involved TCF2, TCF12, ADMA10 and AQP9, might be associated with mental retardation. We delineate the precise structures of the derivative chromosomes, chromosome duplication origin and possible molecular mechanisms for aberrant phenotypes by combining NGS data with conventional techniques. PMID:27218255

  12. Mapping Breakpoints of Complex Chromosome Rearrangements Involving a Partial Trisomy 15q23.1-q26.2 Revealed by Next Generation Sequencing and Conventional Techniques.

    Directory of Open Access Journals (Sweden)

    Qiong Pan

    Full Text Available Complex chromosome rearrangements (CCRs, which are rather rare in the whole population, may be associated with aberrant phenotypes. Next-generation sequencing (NGS and conventional techniques, could be used to reveal specific CCRs for better genetic counseling. We report the CCRs of a girl and her mother, which were identified using a combination of NGS and conventional techniques including G-banding, fluorescence in situ hybridization (FISH and PCR. The girl demonstrated CCRs involving chromosomes 3 and 8, while the CCRs of her mother involved chromosomes 3, 5, 8, 11 and 15. HumanCytoSNP-12 Chip analysis identified a 35.4 Mb duplication on chromosome 15q21.3-q26.2 in the proband and a 1.6 Mb microdeletion at chromosome 15q21.3 in her mother. The proband inherited the rearranged chromosomes 3 and 8 from her mother, and the duplicated region on chromosome 15 of the proband was inherited from the mother. Approximately one hundred genes were identified in the 15q21.3-q26.2 duplicated region of the proband. In particular, TPM1, SMAD6, SMAD3, and HCN4 may be associated with her heart defects, and HEXA, KIF7, and IDH2 are responsible for her developmental and mental retardation. In addition, we suggest that a microdeletion on the 15q21.3 region of the mother, which involved TCF2, TCF12, ADMA10 and AQP9, might be associated with mental retardation. We delineate the precise structures of the derivative chromosomes, chromosome duplication origin and possible molecular mechanisms for aberrant phenotypes by combining NGS data with conventional techniques.

  13. Effect of leucovorin (folinic acid on the developmental quotient of children with Down's syndrome (trisomy 21 and influence of thyroid status.

    Directory of Open Access Journals (Sweden)

    Henri Blehaut

    Full Text Available BACKGROUND: Seven genes involved in folate metabolism are located on chromosome 21. Previous studies have shown that folate deficiency may contribute to mental retardation in Down's syndrome (DS. METHODOLOGY: We investigated the effect of oral folate supplementation (daily dose of 1.0+/-0.3 mg/kg on cognitive functions in DS children, aged from 3 to 30 months. They received 1 mg/kg leucovorin or placebo daily, for 12 months, in a single-centre, randomised, double-blind study. Folinic acid (leucovorin, LV was preferred to folic acid as its bioavailability is higher. The developmental age (DA of the patients was assessed on the Brunet-Lezine scale, from baseline to the end of treatment. RESULTS: The intent-to-treat analysis (113 patients did not show a positive effect of leucovorin treatment. However, it identified important factors influencing treatment effect, such as age, sex, and concomitant treatments, including thyroid treatment in particular. A per protocol analysis was carried out on patients evaluated by the same examiner at the beginning and end of the treatment period. This analysis of 87 patients (43 LV-treated vs. 44 patients on placebo revealed a positive effect of leucovorin on developmental age (DA. DA was 53.1% the normal value with leucovorin and only 44.1% with placebo (p<0.05. This positive effect of leucovorin was particularly strong in patients receiving concomitant thyroxin treatment (59.5% vs. 41.8%, p<0.05. No adverse event related to leucovorin was observed. CONCLUSION: These results suggest that leucovorin improves the psychomotor development of children with Down's syndrome, at least in some subgroups of the DS population, particularly those on thyroxin treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00294593.

  14. Extending Newtonian Dynamics to Include Stochastic Processes

    Science.gov (United States)

    Zak, Michail

    2009-01-01

    A paper presents further results of continuing research reported in several previous NASA Tech Briefs articles, the two most recent being Stochastic Representations of Chaos Using Terminal Attractors (NPO-41519), [Vol. 30, No. 5 (May 2006), page 57] and Physical Principle for Generation of Randomness (NPO-43822) [Vol. 33, No. 5 (May 2009), page 56]. This research focuses upon a mathematical formalism for describing post-instability motions of a dynamical system characterized by exponential divergences of trajectories leading to chaos (including turbulence as a form of chaos). The formalism involves fictitious control forces that couple the equations of motion of the system with a Liouville equation that describes the evolution of the probability density of errors in initial conditions. These stabilizing forces create a powerful terminal attractor in probability space that corresponds to occurrence of a target trajectory with probability one. The effect in configuration space (ordinary three-dimensional space as commonly perceived) is to suppress exponential divergences of neighboring trajectories without affecting the target trajectory. As a result, the post-instability motion is represented by a set of functions describing the evolution of such statistical quantities as expectations and higher moments, and this representation is stable.

  15. Alternating phase focussing including space charge

    International Nuclear Information System (INIS)

    Longitudinal stability can be obtained in a non-relativistic drift tube accelerator by traversing each gap as the rf accelerating field rises. However, the rising accelerating field leads to a transverse defocusing force which is usually overcome by magnetic focussing inside the drift tubes. The radio frequency quadrupole is one way of providing simultaneous longitudinal and transverse focusing without the use of magnets. One can also avoid the use of magnets by traversing alternate gaps between drift tubes as the field is rising and falling, thus providing an alternation of focussing and defocusing forces in both the longitudinal and transverse directions. The stable longitudinal phase space area is quite small, but recent efforts suggest that alternating phase focussing (APF) may permit low velocity acceleration of currents in the 100-300 ma range. This paper presents a study of the parameter space and a test of crude analytic predictions by adapting the code PARMILA, which includes space charge, to APF. 6 refs., 3 figs

  16. Langevin simulations of QCD, including fermions

    International Nuclear Information System (INIS)

    We encounter critical slow down in updating when xi/a -> infinite and in matrix inversion (needed to include fermions) when msub(q)a -> 0. A simulation that purports to solve QCD numerically will encounter these limits, so to face the challenge in the title of this workshop, we must cure the disease of critical slow down. Physically, this critical slow down is due to the reluctance of changes at short distances to propagate to large distances. Numerically, the stability of an algorithm at short wavelengths requires a (moderately) small step size; critical slow down occurs when the effective long wavelength step size becomes tiny. The remedy for this disease is an algorithm that propagates signals quickly throughout the system; i.e. one whose effective step size is not reduced for the long wavelength conponents of the fields. (Here the effective ''step size'' is essentially an inverse decorrelation time.) To do so one must resolve various wavelengths of the system and modify the dynamics (in CPU time) of the simulation so that all modes evolve at roughly the same rate. This can be achieved by introducing Fourier transforms. I show how to implement Fourier acceleration for Langevin updating and for conjugate gradient matrix inversion. The crucial feature of these algorithms that lends them to Fourier acceleration is that they update the lattice globally; hence the Fourier transforms are computed once per sweep rather than once per hit. (orig./HSI)

  17. SEEPAGE MODEL FOR PA INCLUDING DRIFT COLLAPSE

    Energy Technology Data Exchange (ETDEWEB)

    C. Tsang

    2004-09-22

    The purpose of this report is to document the predictions and analyses performed using the seepage model for performance assessment (SMPA) for both the Topopah Spring middle nonlithophysal (Tptpmn) and lower lithophysal (Tptpll) lithostratigraphic units at Yucca Mountain, Nevada. Look-up tables of seepage flow rates into a drift (and their uncertainty) are generated by performing numerical simulations with the seepage model for many combinations of the three most important seepage-relevant parameters: the fracture permeability, the capillary-strength parameter 1/a, and the percolation flux. The percolation flux values chosen take into account flow focusing effects, which are evaluated based on a flow-focusing model. Moreover, multiple realizations of the underlying stochastic permeability field are conducted. Selected sensitivity studies are performed, including the effects of an alternative drift geometry representing a partially collapsed drift from an independent drift-degradation analysis (BSC 2004 [DIRS 166107]). The intended purpose of the seepage model is to provide results of drift-scale seepage rates under a series of parameters and scenarios in support of the Total System Performance Assessment for License Application (TSPA-LA). The SMPA is intended for the evaluation of drift-scale seepage rates under the full range of parameter values for three parameters found to be key (fracture permeability, the van Genuchten 1/a parameter, and percolation flux) and drift degradation shape scenarios in support of the TSPA-LA during the period of compliance for postclosure performance [Technical Work Plan for: Performance Assessment Unsaturated Zone (BSC 2002 [DIRS 160819], Section I-4-2-1)]. The flow-focusing model in the Topopah Spring welded (TSw) unit is intended to provide an estimate of flow focusing factors (FFFs) that (1) bridge the gap between the mountain-scale and drift-scale models, and (2) account for variability in local percolation flux due to

  18. Including lifestyle medicine in undergraduate medical curricula

    Directory of Open Access Journals (Sweden)

    Edward Phillips

    2015-02-01

    Full Text Available Purpose: Currently, there is no model to integrate the discipline of lifestyle medicine (LM into undergraduate medical education. Furthermore, there are no guidelines, validated assessment tools, or evaluation or implementation plans in place. Background: The World Health Organization predicts that by 2020, two-thirds of disease worldwide will be the result of poor lifestyle choices. Fewer than 50% of US primary care physicians routinely provide specific guidance on nutrition, physical activity, or weight control. Methods: We are establishing a plan to integrate LM into medical school education in collaboration with the investing stakeholders, including medical school deans and students, medical curriculum developers and researchers, medical societies, governing bodies, and policy institutes. Three planning and strategy meetings are being held to address key areas of focus – with a particular interest in nutrition, physical activity, student self-care, and behavior change – to develop specific implementation guidelines and landmarks. Results: After the first two meetings, the proposed areas of focus were determined to be: 1 supporting of deans and key personnel, 2 creation of federal and state policy commitments, 3 use of assessment as a driver of LM, 4 provision of high-quality evidence-based curricular material on an easily navigated site, and 5 engaging student interest. Implementation strategies for each focus area will be addressed in an upcoming planning meeting in early 2015. Conclusion: This initiative is expected to have important public health implications by efficiently promoting the prevention and treatment of non-communicable chronic disease with a scalable and sustainable model to educate physicians in training and practice.

  19. Compact Radar Transceiver with Included Calibration

    Science.gov (United States)

    McLinden, Matthew; Rincon, Rafael

    2013-01-01

    The Digital Beamforming Synthetic Aperture Radar (DBSAR) is an eight-channel phased array radar system that employs solid-state radar transceivers, a microstrip patch antenna, and a reconfigurable waveform generator and processor unit. The original DBSAR transceiver design utilizes connectorized electronic components that tend to be physically large and heavy. To achieve increased functionality in a smaller volume, PCB (printed circuit board) transceivers were designed to replace the large connectorized transceivers. One of the most challenging problems designing the transceivers in a PCB format was achieving proper performance in the calibration path. For a radar loop-back calibration path, a portion of the transmit signal is coupled out of the antenna feed and fed back into the receiver. This is achieved using passive components for stability and repeatability. Some signal also leaks through the receive path. As these two signal paths are correlated via an unpredictable phase, the leakage through the receive path during transmit must be 30 dB below the calibration path. For DBSAR s design, this requirement called for a 100-dB isolation in the receiver path during transmit. A total of 16 solid-state L-band transceivers on a PCB format were designed. The transceivers include frequency conversion stages, T/R switching, and a calibration path capable of measuring the transmit power-receiver gain product during transmit for pulse-by-pulse calibration or matched filtering. In particular, this calibration path achieves 100-dB isolation between the transmitted signal and the low-noise amplifier through the use of a switching network and a section of physical walls achieving attenuation of radiated leakage. The transceivers were designed in microstrip PCBs with lumped elements and individually packaged components for compactness. Each transceiver was designed on a single PCB with a custom enclosure providing interior walls and compartments to isolate transceiver

  20. Ocean storage, including costs and risks

    International Nuclear Information System (INIS)

    The long-term effectiveness of ocean storage will have to be based on theoretical understanding and models as there is no way to perform experiments on the required time and space scales for outgassing estimation. Based on observations of tracer behavior, the ventilation time of deep water has been revealed. Calibrated and constrained by these results, most of the OGCMs tell us that CO2 injected into the thermohaline circulation would not come back to the atmosphere in more than several hundred years. There are two types of concepts of ocean storage: one is a lake type concept to keep the CO2 at the ocean floor or a depression site as long as possible, and the other is to inject CO2 into the deep waters so that it is dispersed as quickly as possible. The technological concepts so far for implementation with minimum environmental impacts are much elaborated based on laboratory and computer experiments incorporating the key understanding of the CO2 clathrate properties attained in this decade. The frequently addressed concern of this technology includes the ecological modification of the ocean system. But even in the business-as-usual release of CO2 into the atmosphere, some modification might be foreseen in the deep ocean environment and could be inevitable not caused by the climate change but by the direct influence of the increase in the CO2 concentration in deep waters in future. We cannot stop the CO2 invasion into the deep ocean due to the existing of the excess CO2 in the atmosphere. Whichever release method is used, carbon dioxide we are releasing to the atmosphere now will find its way into the deep oceans. Hence, the right scientific question is whether there exist additional risks to the deep sea environment associated with this technology. If we accept the target of a stabilization level of the atmospheric concentration of CO2, our generation's commitment to the CO2 futures anyway extends to the modification of the deep sea environment induced by the

  1. An Integrated Biochemistry Laboratory, Including Molecular Modeling

    Science.gov (United States)

    Hall, Adele J. Wolfson Mona L.; Branham, Thomas R.

    1996-11-01

    The dilemma of designing an advanced undergraduate laboratory lies in the desire to teach and reinforce basic principles and techniques while at the same time exposing students to the excitement of research. We report here on a one-semester, project-based biochemistry laboratory that combines the best features of a cookbook approach (high success rate, achievement of defined goals) with those of an investigative, discovery-based approach (student involvement in the experimental design, excitement of real research). Individual modules may be selected and combined to meet the needs of different courses and different institutions. The central theme of this lab is protein purification and design. This laboratory accompanies the first semester of biochemistry (Structure and Function of Macromolecules, a course taken mainly by junior and senior chemistry and biological chemistry majors). The protein chosen as the object of study is the enzyme lysozyme, which is utilized in all projects. It is suitable for a student lab because it is easily and inexpensively obtained from egg white and is extremely stable, and its high isoelectric point (pI = 11) allows for efficient separation from other proteins by ion-exchange chromatography. Furthermore, a literature search conducted by the resourceful student reveals a wealth of information, since lysozyme has been the subject of numerous studies. It was the first enzyme whose structure was determined by crystallography (1). Hendrickson et al. (2) have previously described an intensive one-month laboratory course centered around lysozyme, although their emphasis is on protein stability rather than purification and engineering. Lysozyme continues to be the focus of much exciting new work on protein folding and dynamics, structure and activity (3 - 5). This lab course includes the following features: (i) reinforcement of basic techniques, such as preparation of buffers, simple enzyme kinetics, and absorption spectroscopy; (ii

  2. The Dianosis Value of Prenatal Ultrasound Screening Combined with Prenatal Maternal Serum Markers Detecting in Trimester Pregnancy for the 21 - trisomy Syndrome%中孕B超产前检查联合母血清标记物对21-三体综合征的临床诊断价值

    Institute of Scientific and Technical Information of China (English)

    李洁; 陈大雁; 胡桂朗; 荆志敏

    2011-01-01

    Objective: To explore the feasibility, effectiveness and necessity of the prenatal ultrasound screenings,combined with the content inspection of the mothers' prenatal maternal serum markers:in trimester pregnancy Alpha-fetoprotein ( AFP), free estriol ( uE3 ), total serum β human chorionic gonadotropin ( hCG) in the 21 -trisomy syndrome. Method: We summarized the detection rate of the 21 -trisomy syndrome by prenatal ultrasound screening and the prenatal maternal serum markers. Result: The detection rate in terms of the positive signs of the prenatal ultrasound screening in trimester pregnancy combined with the prenatal maternal serum markers in the 21-trisomy syndrome diagnosis was 80%-90%. Conclusion:The prenatal ultrasound screening in trimester pregnancy combined with prenatal maternal serum markers in the 21trisomy syndrome diagnosis is a non-invasive checking method, not only can reduce the abnormal or deformed children are born, can also reduce the invasive inspection; It has the davantage of clinically simple,application and testing of a wide range of safe and effective, cost-effective, with higher screening detection rate, and reduce the intrusion caused by the check normal fetal abortion rate.%目的:探讨中孕B超产前检查出现阳性征,及联合母体血清标记物指标:甲胎蛋白(AFP)、游离雌三醇(uE3)、血清总β绒毛膜促性腺激素(hCG)的含量检查对21-三体综合征的产前筛查和诊断的可行性、有效性和必要性.方法:回顾了中孕B超产前检查联合母血清标记物对21-三体综合征检出率.结果:中孕B超产前检查的阳性征,联合母体血清标记物检查指标对21三体综合征检出率高达80%-90%.结论:中孕超声检查,及联合母血清标记物进行唐氏综合征胎儿筛查是一种非侵入性的检查方法,不但可以减少异常或畸型儿童出生,提高人口素质,也可以减少侵入性的检查;且具有临床操作简便、应用范围和检验范围面广

  3. Les sages-femmes et le dépistage de la trisomie 21 : connaissances et transmission de l'information. Étude descriptive auprès des sages-femmes de deux régions françaises

    OpenAIRE

    Le Roux, Louise

    2013-01-01

    Le consentement éclairé est essentiel pour que le dépistage de la trisomie 21 soit éthiquement acceptable. Cependant, la littérature dévoile des lacunes chez les patientes vis-à-vis de ce dépistage, ce qui remet en question le choix éclairé de la femme enceinte à le pratiquer. Or, à l'origine de l'information se trouvent les professionnels de la périnatalité et notamment les sages-femmes. Ainsi, nous sommes en mesure de nous demander quelles connaissances ont les sages-femmes de ce dépistage ...

  4. Ionic liquids, electrolyte solutions including the ionic liquids, and energy storage devices including the ionic liquids

    Energy Technology Data Exchange (ETDEWEB)

    Gering, Kevin L.; Harrup, Mason K.; Rollins, Harry W.

    2015-12-08

    An ionic liquid including a phosphazene compound that has a plurality of phosphorus-nitrogen units and at least one pendant group bonded to each phosphorus atom of the plurality of phosphorus-nitrogen units. One pendant group of the at least one pendant group comprises a positively charged pendant group. Additional embodiments of ionic liquids are disclosed, as are electrolyte solutions and energy storage devices including the embodiments of the ionic liquid.

  5. Social Early Stimulation of Trisomy-21 Babies

    Science.gov (United States)

    Aparicio, Maria Teresa Sanz; Balana, Javier Menendez

    2003-01-01

    This study was initiated with twenty Down's syndrome babies to verify whether subjects undergoing social early stimulation would benefit from this type of treatment. An experimental study was designed with two training groups: visual or written instructions. The analyses of the results established statistically significant differences in the…

  6. Patau sendromu (trisomi 13): olgu sunumu

    OpenAIRE

    Bahçe, Selda; Çetin, Meral; Yıldız, Çağlar; Özdemir, Öztürk

    2010-01-01

    ÖzetPatau sendromu canlı doğumlarda 1/12000-29000 oranında görülmektedir. Prenatal tanı önem göstermekle birlikte ileri anne yaşı ile bu sendromun görülme sıklığı artmaktadır. Trizomi 13 ya da Patau sendromu, Trizomi 21 (Down sendromu) ve Trizomi 18’den (Edward sendromu) sonra en yaygın olarak görülen üçüncü otozomal trizomili kromozom düzensizliğidir. Bu çalışmamızda 22 haftalık gebeliği bulunan hastanın yap...

  7. Correspondence between future-included and future-not-included theories

    CERN Document Server

    Nagao, Keiichi

    2013-01-01

    We briefly review the correspondence principle proposed in our previous paper, which claims that if we regard a matrix element defined in terms of the future state at time $T_B$ and the past state at time $T_A$ as an expectation value in the complex action theory whose path runs over not only past but also future, the expectation value at the present time $t$ of a future-included theory for large $T_B-t$ and large $t-T_A$ corresponds to that of a future-not-included theory with a proper inner product for large $t-T_A$. This correspondence principle suggests that the future-included theory is not excluded phenomenologically.

  8. Launch Lock Assemblies Including Axial Gap Amplification Devices and Spacecraft Isolation Systems Including the Same

    Science.gov (United States)

    Barber, Tim Daniel (Inventor); Hindle, Timothy (Inventor); Young, Ken (Inventor); Davis, Torey (Inventor)

    2014-01-01

    Embodiments of a launch lock assembly are provided, as are embodiments of a spacecraft isolation system including one or more launch lock assemblies. In one embodiment, the launch lock assembly includes first and second mount pieces, a releasable clamp device, and an axial gap amplification device. The releasable clamp device normally maintains the first and second mount pieces in clamped engagement; and, when actuated, releases the first and second mount pieces from clamped engagement to allow relative axial motion there between. The axial gap amplification device normally residing in a blocking position wherein the gap amplification device obstructs relative axial motion between the first and second mount pieces. The axial gap amplification device moves into a non-blocking position when the first and second mount pieces are released from clamped engagement to increase the range of axial motion between the first and second mount pieces.

  9. Understanding the Limitations of Circulating Cell Free Fetal DNA: An Example of Two Unique Cases.

    Science.gov (United States)

    Clark-Ganheart, Cecily A; Iqbal, Sara N; Brown, Donna L; Black, Susan; Fries, Melissa H

    2014-05-01

    Circulating cell free fetal DNA (cffDNA) is an effective screening modality for fetal aneuploidy. We report two cases of false positive results. The first case involves a female, with self-reported Down syndrome. CffDNA returned positive for trisomy 18 leading to a maternal diagnosis of mosaicism chromosome 18 with normal fetal karyotype. The second case involves a patient with an anomalous fetal ultrasound and cffDNA positive for trisomy 13. Amniocentesis demonstrated a chromosome 8p duplication/deletion. False positive cffDNA may arise in clinical scenarios where diagnostic testing is clearly indicated. Practitioners should recognize the limitations of cffDNA. PMID:25298847

  10. Stable variants of sperm aneuploidy among healthy men show associations between germinal and somatic aneuploidy

    Czech Academy of Sciences Publication Activity Database

    Rubeš, Jiří; Vozdová, M.; Řezáčová, 0.; Robbins, W.; Perreault, S.; Wyrobek, A.

    Elsevier. Roč. 483, č. 1 (2001), s. Supplement 1. ISSN 0027-5107. [International Conference on Environmental Mutagens /8./. 21.10.2001-26.10.2001, Shizuoka] Institutional research plan: CEZ:AV0Z5039906 Keywords : chromosomal abnormalities Subject RIV: DN - Health Impact of the Environment Quality

  11. A Case Report of Myelodysplastic/Myeloproliferative Disease Unclassifiable with Karyotype Aberration of Trisomy 8 and JAK2 Mutation%+8伴JAK2突变的骨髓增生异常/骨髓增殖性疾病不能分类1例

    Institute of Scientific and Technical Information of China (English)

    刘鲲; 阴常欣; 陈学东; 周雪云; 郭坤元

    2012-01-01

    本研究探讨1例骨髓增生异常/骨髓增殖性疾病不能分类(MDS/MPD-U)患者的临床特征、染色体核型与JAK2基因突变发生的关系.利用骨髓组织学活检、染色体核型分析技术、ARMS-PCR等方法,观察该MDS/MPD-U患者的临床特征、染色体核型、JAK2基因突变情况.结果表明,患者骨髓有典型的小巨核细胞、血小板增多、8号染色体三体异常、JAK2 V617F基因突变.结论:该患者符合MDS/MPD-U的诊断,伴有+8,JAK2 V617F基因突变,为进一步研究染色体核型异常与JAK2 V617F基因突变两种分子事件之间的相关性及对MDS/MPD-U预后的影响提供依据.%This study aimed to investigate the relationship between clinical features of myelodysplastic/ myeloproliferative disease, unclassifiable(MDS/MPD-U), karyotype of chromosome and JAK2 mutation in 1 case. The clinical features, karyotype and JAK2 mutation of the patient with MDS/MPD-U were studied by means of bone marrow biopsy, karyotype analysis and ARMS-PCR technique. The results indicated that the typical micromegkaryocytes and thrombocytosis, karyotype aberration of trisomy 8 as well as JAK2 V617F mutation were found in this patient. It is concluded that the patient was diagnosed as MDS/MPD-U with trisomy 8 and JAK2 V617F mutation. The data of this patient will provide evidence for studying correlation of chromosome karyotype aberration with JAK2 V617F mutation and for evaluating prognosis of MDS/MPD-U.

  12. First-Trimester Combined Screening Is Effective for the Detection of Unbalanced Chromosomal Translocations at 11 to 12 Weeks of Gestation

    OpenAIRE

    Huang, ShangYu; Chang, Chialin; Cheng, PoJen; Hsiao, ChingHua; Soong, YungKuei; Duan, Tao

    2014-01-01

    The first trimester combined screening, which analyzes fetal nuchal translucency and levels of free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein A (PAPP-A) in maternal serum, is routinely used to detect abnormal pregnancies associated with Down syndrome and other trisomy aneuploidies. Based on the hypothesis that major chromosomal translocations could lead to similar biochemical and developmental outcomes during early embryo development, we compared these mar...

  13. An unusual combination of trisomy 21 and partial trisomy 5q.

    OpenAIRE

    Kim, C J; Chi, J. G.; K. H. Lee; Lee, C. K.; Yoo, M. S.; Paik, Y K

    1992-01-01

    The authors describe a male newborn with multiple congenital anomalies; craniofacial dysmorphism, bilateral cleft palate and lip, ambiguous external genitalia with absence of phallus, ventricular septal defect, agenesis of olfactory bulbs, and presence of small round cells simulating migration defect in the cerebellar white matter. Cytogenetic study demonstrated a chromosomal constitution of 47,XY, +21, +5q. Its pathological significance compared with Down's syndrome and hitherto reported par...

  14. Towards Early Biochemical screening for Fetal Aneupliody in the First Trimester

    DEFF Research Database (Denmark)

    Tørring, Niels

    2011-01-01

    trimester screening and the blood sample taken between 7 weeks + 5 days to 13 weeks + 6 days from November 2003 to March 2011. Results: 159 out of 173 cases of trisomy 21 were diagnosed in the first trimester screening (detection rate 92%). When the blood sample was taken before the 10th gestational week......, the detection rate of trisomy 21 was 96% (99 out of 103), whereas 86% were detected (50 out of 60) after 10th week (Chi square = 0.03). For trisomy 18 and trisomy 13, 26 out of 32 (81%) were detected before 10th gestational week, and 9 out of 13 (69%) after the 10th gestational week (N.S). Conclusions......: Screening for fetal aneuploidy can be performed with good results with the blood sample taken as early as the 7th week of gestation. Taking the blood sample before the 10th gestational week showed a high detection rate of fetal trisomy 21, with no difference in the detection of fetal trisomy 18, 13 or...

  15. First Trimester Maternal Serum Screening Using Biochemical Markers PAPP-A and Free β-hCG for Down Syndrome, Patau Syndrome and Edward Syndrome.

    Science.gov (United States)

    Shiefa, S; Amargandhi, M; Bhupendra, J; Moulali, S; Kristine, T

    2013-01-01

    The first trimester screening programme offers a noninvasive option for the early detection of aneuploidy pregnancies. This screening is done by a combination of two biochemical markers i.e. serum free β-human chorionic gonadotrophin (free β-hCG) and pregnancy associated plasma protein A (PAPP-A), maternal age and fetal nuchal translucency (NT) thickness at 11 + 0-13 + 6 weeks of gestation. A beneficial consequence of screening is the early diagnosis or trisomies 21, 18 and 13. At 11 + 0-13 + 6 weeks, the relative prevalence of trisomies 18 and 13 to trisomy 21 are found to be one to three and one to seven, respectively. All three trisomies are associated with increased maternal age, increased fetal NT and decreased PAPP-A, but in trisomy 21 serum free β-hCG is increased whereas in trisomies 18 and 13 free β-hCG is decreased. PMID:24381414

  16. 评估人类精子中原位非整倍体:引物原位杂交和缩氨酸核酸荧光原位杂交技术的使用%In situ aneuploidy assessment in human sperm: the use of primed in situ and peptide nucleic acid-fluorescence in situ hybridization techniques

    Institute of Scientific and Technical Information of China (English)

    F.Pellestor

    2006-01-01

    引物原位杂交(PRINS)和缩氨酸核酸荧光原位杂交(PNA-FISH)技术都可替代传统的荧光原位杂交(FISH)技术,用于染色体的研究.PRINS反应的基本物是DNA聚合酶和引物原位扩展反应中的标引核苷.缩氨酸核酸探针是合成的不带电聚酰胺主链的DNA类似物.这两种技术特异、快速、识别能力强的优点使它们细胞遗传学研究中很受欢迎.它们在人类精子研究中的应用使男性配子的染色体筛选过程得到新的快速发展,成为男性配子非整倍体原位评估中的FISH技术的有效补充.%Both the primed in situ (PRINS) and the peptide nucleic acid-fluorescence in situ hybridization (PNA-FISH)techniques constitute alternatives to the conventional (fluorescence in situ hybridization, FISH) procedure for chromosomal investigations. The PRINS reaction is based on the use of a DNA polymerase and labeled nucleotide in an in situ primer extension reaction. Peptide nucleic acid probes are synthetic DNA analogs with uncharged polyamide backbones. The two procedures present several advantages (specificity, rapidity and discriminating ability) that make them very attractive for cytogenetic purposes. Their adaptation to human spermatozoa has allowed the development of new and fast procedures for the chromosomal screening of male gametes and has provided efficient complements to FISH for in situ assessment of aneuploidy in male gametes.

  17. Interphase cytogenetics of workers exposed to benzene

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, L.; Wang, Yunxia; Venkatesh, P. [Univ. of California, Berkeley, CA (United States)] [and others

    1996-12-01

    Fluorescence in situ hybridization (FISH) is a powerful new technique that allows numerical chromosome aberrations (aneuploidy) to be detected in interphase cells. In previous studies, FISH has been used to demonstrate that the benzene metabolites hydroquinone and 1,2,4-benzenetriol induce aneuploidy of chromosomes 7 and 9 in cultures of human cells. In the present study, we used an interphase FISH procedure to perform cytogenetic analyses on the blood cells of 43 workers exposed to benzene (median=31 ppm, 8-hr time-weighted average) and 44 matched controls from Shanghai, China. High benzene exposure (>31 ppm, n=22) increased the hyperdiploid frequency of chromosome 9 (p<0.01), but lower exposure (<31 ppm, n=21) did not. Trisomy 9 was the major form of benzene-induced hyperdiploidy. The level of hyperdiploidy in exposed workers correlated with their urinary phenol level (r= 0.58, p < 0.0001), a measure of internal benzene close. A significant correlation was also found between hyperdiploicly and decreased absolute lymphocyte count, an indicator of benzene hematotoxicity, in the exposed group (r=-0.44, p=0.003) but not in controls (r=-0.09, P=0.58). These results show that high benzene exposure induces aneuploidy of chromosome 9 in nondiseased individuals, with trisomy being the most prevalent form. They further highlight the usefulness of interphase cytogenetics and FISH for the rapid and sensitive detection of aneuploidy in exposed human populations. 35 refs., 3 figs., 2 tabs.

  18. Faults of Europe including Turkey (flt4_2l)

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This coverage includes arcs that describe faults found in the surface outcrops of bedrock of Europe including Turkey (Albania, Andorra, Austria, Belgium, Bosnia and...

  19. Should Relational Aggression Be Included in DSM-V?

    Science.gov (United States)

    Keenan, Kate; Coyne, Claire; Lahey, Benjamin B.

    2008-01-01

    The study examines whether relational aggression should be included in DSM-V disruptive behavior disorders. The results conclude that some additional information is gathered from assessing relational aggression but not enough to be included in DSM-V.

  20. Partially ionized plasmas including the third symposium on uranium plasmas

    Energy Technology Data Exchange (ETDEWEB)

    Krishnan, M. [ed.

    1976-09-01

    Separate abstracts are included for 28 papers on electrically generated plasmas, fission generated plasmas, nuclear pumped lasers, gaseous fuel reactor research, and applications. Five papers have been previously abstracted and included in ERA.