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Sample records for syndrome molecular genetic

  1. Alport syndrome. Molecular genetic aspects

    DEFF Research Database (Denmark)

    Hertz, Jens Michael

    2009-01-01

    a highly efficient and sensitive molecular diagnostic approach for analysing the COL4A5 gene in putative AS cases. Based on the present results and the litterature, an algorithm for molecular genetic analysis of the COL4A5 gene is suggested. The overall mutation detection rate was found to be 53......Alport syndrome (AS) is a progressive renal disease that is characterised by hematuria and progressive renal failure, and often accompanied by progressive high-tone sensorineural hearing loss and ocular changes in form of macular flecks and lenticonus. AS is a genetic heterogenous disease, and X...... practice for carrier detection and prenatal diagnosis, in order to be able to offer a better genetic counselling to the families. Knowledge of a possible correlation between genotype and phenotype can be of help in predicting the prognosis. Samples from 135 probands suspected of AS and 359...

  2. Molecular genetic analysis of Down syndrome.

    Science.gov (United States)

    Patterson, David

    2009-07-01

    Down syndrome (DS) is caused by trisomy of all or part of human chromosome 21 (HSA21) and is the most common genetic cause of significant intellectual disability. In addition to intellectual disability, many other health problems, such as congenital heart disease, Alzheimer's disease, leukemia, hypotonia, motor disorders, and various physical anomalies occur at an elevated frequency in people with DS. On the other hand, people with DS seem to be at a decreased risk of certain cancers and perhaps of atherosclerosis. There is wide variability in the phenotypes associated with DS. Although ultimately the phenotypes of DS must be due to trisomy of HSA21, the genetic mechanisms by which the phenotypes arise are not understood. The recent recognition that there are many genetically active elements that do not encode proteins makes the situation more complex. Additional complexity may exist due to possible epigenetic changes that may act differently in DS. Numerous mouse models with features reminiscent of those seen in individuals with DS have been produced and studied in some depth, and these have added considerable insight into possible genetic mechanisms behind some of the phenotypes. These mouse models allow experimental approaches, including attempts at therapy, that are not possible in humans. Progress in understanding the genetic mechanisms by which trisomy of HSA21 leads to DS is the subject of this review.

  3. The Molecular Genetics of Restless Legs Syndrome.

    Science.gov (United States)

    Rye, David B

    2015-09-01

    Restless legs syndrome (RLS) is a common sensorimotor trait defined by symptoms that interfere with sleep onset and maintenance in a clinically meaningful way. Nonvolitional myoclonus while awake and asleep is a sign of the disorder and an informative endophenotype. The genetic contributions to RLS/periodic leg movements are substantial, are among the most robust defined to date for a common disease, and account for much of the variance in disease expressivity. The disorder is polygenic, as revealed by recent genome-wide association studies. Experimental studies are revealing mechanistic details of how these common variants might influence RLS expressivity. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Genetic analysis of CHARGE syndrome identifies overlapping molecular biology.

    Science.gov (United States)

    Moccia, Amanda; Srivastava, Anshika; Skidmore, Jennifer M; Bernat, John A; Wheeler, Marsha; Chong, Jessica X; Nickerson, Deborah; Bamshad, Michael; Hefner, Margaret A; Martin, Donna M; Bielas, Stephanie L

    2018-01-04

    PurposeCHARGE syndrome is an autosomal-dominant, multiple congenital anomaly condition characterized by vision and hearing loss, congenital heart disease, and malformations of craniofacial and other structures. Pathogenic variants in CHD7, encoding adenosine triphosphate-dependent chromodomain helicase DNA binding protein 7, are present in the majority of affected individuals. However, no causal variant can be found in 5-30% (depending on the cohort) of individuals with a clinical diagnosis of CHARGE syndrome.MethodsWe performed whole-exome sequencing (WES) on 28 families from which at least one individual presented with features highly suggestive of CHARGE syndrome.ResultsPathogenic variants in CHD7 were present in 15 of 28 individuals (53.6%), whereas 4 (14.3%) individuals had pathogenic variants in other genes (RERE, KMT2D, EP300, or PUF60). A variant of uncertain clinical significance in KDM6A was identified in one (3.5%) individual. The remaining eight (28.6%) individuals were not found to have pathogenic variants by WES.ConclusionThese results demonstrate that the phenotypic features of CHARGE syndrome overlap with multiple other rare single-gene syndromes. Additionally, they implicate a shared molecular pathology that disrupts epigenetic regulation of multiple-organ development.GENETICS in MEDICINE advance online publication, 4 January 2018; doi:10.1038/gim.2017.233.

  5. [Wolfram syndrome: clinical features, molecular genetics of WFS1 gene].

    Science.gov (United States)

    Tanabe, Katsuya; Matsunaga, Kimie; Hatanaka, Masayuki; Akiyama, Masaru; Tanizawa, Yukio

    2015-02-01

    Wolfram syndrome(WFS: OMIM 222300) is a rare recessive neuro-endocrine degenerative disorder, known as DIDMOAD(Diabetes Insipidus, early-onset Diabetes Mellitus, Optic Atrophy and Deafness) syndrome. Most affected individuals carry recessive mutations in the Wolfram syndrome 1 gene(WFS1). The WFS1 protein is an endoplasmic reticulum(ER) embedded protein, which functions in ER calcium homeostasis and unfolded protein responses. Dysregulation of these cellular processes results in the development of ER stress, leading to apoptosis. In addition, abundantly present WFS1 protein in insulin secretory granules plays a role in the intra-granular acidification. However, the phenotypic pleiomorphism and molecular complexity of this disease limit the understanding of WFS. Here we review clinical features, molecular mechanisms and mutations of WFS1 gene that relate to this syndrome.

  6. Clinical and Molecular Genetic Features of Autoinflammatory Syndromes in Children

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    Е. I. Alexeeva

    2015-01-01

    Full Text Available Objective: Our aim was to study the prevalence and clinical features of autoinflammatory syndromes among patients with systemic juvenile idiopathic arthritis. Methods: A prospective nonrandomized study was conducted. All its members have been studied for mutations in TNFRSF1A and NLRP3 genes by the sequencing method. Results: 90 children (27 boys, 63 girls aged from 1 to 17 (average age 8.2 years, with a guide diagnosis: «Systemic juvenile idiopathic arthritis», were examined. As a result, 10 (14% patients showed mutations in TNFRSF1A gene, leading to the development of TRAPS-syndrome (8 had the most common mutation of R92Q; 3 — not previously described mutations in NLRP3 gene. 2 patients had the diagnosis of CINCA/NOMID Syndrome, 1 — Muckle–Wells Syndrome. In three cases, mutations leading to the development of TRAPS-syndromethe were identified in the first line of descent. Classical examples of autoinflammatory syndromes such as cryopyrin-associated periodic syndrome (CAPS, and tumor necrosis factor receptor associated periodic syndrome (TRAPS. The data about their pathogenesis, clinical features, diagnosis and treatment is presented. Conclusion: It is shown that early detection and adequate treatment of patients with autoinflammatory syndromes, characterized by severe disease and serious prognosis, is difficult due to lack of awareness of pediatricians and unavailability of genetic diagnosis of these syndromes. The necessity of the development of a universal model of the diagnostic algorithm for identification of autoinflammatory syndromes using next-generation sequencing technologies is grounded. 

  7. Ellis-Van Creveld Syndrome: Prenatal Diagnosis, Molecular Analysis and Genetic Counseling

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    Chih-Ping Chen

    2010-12-01

    Conclusion: Prenatal sonographic identification of endocardial cushion defects in association with shortening of the long bones should alert clinicians to the possibility of EvC syndrome and prompt a careful search of hexadactyly of the hands. Molecular analysis of the EVC and EVC2 genes is helpful in genetic counseling in cases with prenatally detected postaxial polydactyly, thoracic narrowness, short limbs and endocardial cushion defects.

  8. Molecular genetic analysis of Prader-Willi and Angelman syndromes

    Energy Technology Data Exchange (ETDEWEB)

    Kokkonen, H.M.; Kahkonen, T.M.; Leisti, J. [Oulu Univ. Central Hospital (Finland)

    1994-09-01

    Angelman (AS) and Prader-Willi (PWS) syndromes are caused by the loss of either maternal (AS) or paternal (PWS) contributions to chromosome 15q11-q13 region, which is subject to genomic imprinting. DNA methylation has been postulated to play a crucial role in genomic imprinting and the diagnostic test used is based on the differential parental methylation of 15q11-q13. We report here the DNA studies of 39 classical PWS and 12 AS patients. For DNA polymorphism and dosage studies we used nine genomic probes and five microsatellite markers specific for chromosome 15. To study the methylation patterns the probes DN34 (D15S9) and PW71 (D15S63), which show a parental-specific DNA methylation imprint, were used. Among the PWS patients, 29 (77%) cases with a deletion belonging to four different size classes and 9 (23%) with maternal uniparental disomy were found, respectively. Of the AS patients, 8 (67%) had a deletion, 1 (8%) paternal uniparental disomy and 3 (25%) biparental inheritance, respectively. Two sibs with biparental disomy showed a typical methylation pattern for AS, indicating that the maternal chromosome 15 carried a paternal methylation imprint. In the DNA methylation analysis the probe PW71 was useful: in our study it detected all deletions and uniparental disomy patients as well as potential imprinting mutations. The probe DN34 couldn`t identify patients which have a deletion outside the D15S9 locus. In the diagnosis of AS and PWS, the differential methylation of the parental 15q11-q13 offers a rapid diagnostic test but does not distinguish between a deletion and uniparental disomy. In our material the probe 4a.1, which detects DNA sequences from both the locus SNRPN (15q12) and SNRPNP1 (6pter-p21), proved to be reliable detecting all deletions. For detection of parental origin of deletion or uniparental disomy, microsatellite markers proved useful.

  9. Molecular genetics of experimental hypertension and the metabolic syndrome: from gene pathways to new therapies

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Kurtz, T. W.

    2007-01-01

    Roč. 49, č. 5 (2007), s. 941-952 ISSN 0194-911X R&D Projects: GA MZd(CZ) NR8545; GA ČR(CZ) GA301/04/0390; GA ČR(CZ) GA301/06/0028 Grant - others:The Howard Hughes Institute(US) HHMI55005624 Institutional research plan: CEZ:AV0Z50110509 Keywords : SHR * CD36 * metabolic syndrome Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.194, year: 2007

  10. Ellis-van Creveld syndrome: prenatal diagnosis, molecular analysis and genetic counseling.

    Science.gov (United States)

    Chen, Chih-Ping; Su, Yi-Ning; Hsu, Chin-Yuan; Chern, Schu-Rern; Tsai, Fuu-Jen; Wu, Pei-Chen; Chen, Po-Tsang; Wang, Wayseen

    2010-12-01

    To present the perinatal findings and molecular genetic analysis of two siblings with Ellis-van Creveld (EvC) syndrome. A 33-year-old woman, gravida 3, para 1, was referred for genetic counseling at 18 gestational weeks because of recurrent fetal skeletal dysplasia. Two years previously, she had delivered a 1,316-g dead male baby at 28 gestational weeks with a karyotype of 46,XY, postaxial polydactyly of the hands, thoracic narrowness, endocardial cushion defects, transposition of the great arteries, shortening of the long bones, malposition of the toes, and hypoplastic nails. During this pregnancy, prenatal ultrasound at 18 gestational weeks revealed shortening of the long bones (equivalent to 15 weeks), postaxial polydactyly of both hands, thoracic narrowness, and endocardial cushion defects. The pregnancy was subsequently terminated, and a 236-g female fetus was delivered with a karyotype of 46,XX, postaxial polydactyly of the hands, thoracic dysplasia, endocardial cushion defects, shortening of the long bones, and malposition of the toes and hypoplastic nails. The phenotype of each of the two siblings was consistent with EVC syndrome. Molecular analysis of the EVC and EVC2 genes revealed heterozygous mutations in the EVC2 gene. A heterozygous deletion mutation of a 26-bp deletion of c.871-2_894del26 encompassing the junction between intron 7 and exon 8 of the EVC2 gene was found in the mother and two siblings, and a heterozygous nonsense mutation of c.1195C >T, p.R399X in exon 10 of the EVC2 gene was found in the father and two siblings. Prenatal sonographic identification of endocardial cushion defects in association with shortening of the long bones should alert clinicians to the possibility of EvC syndrome and prompt a careful search of hexadactyly of the hands. Molecular analysis of the EVC and EVC2 genes is helpful in genetic counseling in cases with prenatally detected postaxial polydactyly, thoracic narrowness, short limbs and endocardial cushion defects

  11. Unambiguous molecular detections with multiple genetic approach for the complicated chromosome 22q11 deletion syndrome

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    Lin Lung-Huang

    2009-02-01

    Full Text Available Abstract Background Chromosome 22q11 deletion syndrome (22q11DS causes a developmental disorder during the embryonic stage, usually because of hemizygous deletions. The clinical pictures of patients with 22q11DS vary because of polymorphisms: on average, approximately 93% of affected individuals have a de novo deletion of 22q11, and the rest have inherited the same deletion from a parent. Methods using multiple genetic markers are thus important for the accurate detection of these microdeletions. Methods We studied 12 babies suspected to carry 22q11DS and 18 age-matched healthy controls from unrelated Taiwanese families. We determined genomic variance using microarray-based comparative genomic hybridization (array-CGH, quantitative real-time polymerase chain reaction (qPCR and multiplex ligation-dependent probe amplification (MLPA. Results Changes in genomic copy number were significantly associated with clinical manifestations for the classical criteria of 22q11DS using MPLA and qPCR (p Conclusion Both MLPA and qPCR could produce a clearly defined range of deleted genomic DNA, whereas there must be a deleted genome that is not distinguishable using MLPA. These data demonstrate that such multiple genetic approaches are necessary for the unambiguous molecular detection of these types of complicated genomic syndromes.

  12. [Genetic and molecular basis for sodium channel-mediated Brugada syndrome].

    Science.gov (United States)

    Barajas-Martínez, Héctor; Hu, Dan; Antzelevitch, Charles

    2013-01-01

    Brugada syndrome is a genetic disease that is characterized by abnormal electrocardiogram findings and an increased risk of sudden cardiac death. This syndrome is linked to mutations in the SCN5A gene in approximately 20% of Brugada syndrome probands. SCN5A encodes the α subunit of the cardiac sodium channel. Studies conducted over the past decade have identified 11 other Brugada syndrome susceptibility genes besides to SCN5A, pointing to genetic heterogeneity of the syndrome. Transmission of the disease shows an autosomal dominant inheritance pattern. This brief review focuses on a reported case of sodium channel-mediated Brugada syndrome, guiding the reader through the process of identification of the genetic variants responsible for the clinically-diagnosed syndrome, mutagenesis to clone SCN5A with and without the 2 variants identified and transfection of the 2 variants into TSA201 cells to determine the functional consequence of these genetic variants on sodium channel expression and function. Copyright © 2013 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

  13. The Marfan syndrome genetics

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    Galina Pungerčič

    2005-05-01

    Full Text Available Background: The Marfan syndrome is an autosomal dominant heritable disorder of connective tissue. It is caused by mutations in the fibrillin-1 gene encoding glycoprotein fibrillin-1, a component of microfibrils of extracellular matrix. Patients with Marfan syndrome show wide spectra of clinical signs, primarily on skeletal, cardiovascular and ocular organ systems. Cardiovascular complications (especially aortic aneurysm and aortic dissection are the most common cause of mortality of Marfan syndrome patients. Discovering genotype-phenotype correlations is complicated because of the large number of mutations reported as well as clinical heterogeneity among individuals with the same mutation. Despite the progress in the knowledge of the molecular nature of Marfan syndrome the diagnosis is still based mainly on the clinical features in the different body systems.Conclusions: Early identification of patient with Marfan syndrome is of considerable importance because of appropriate treatment that can greatly improve life expectancy. Unfortunately, despite the improvement of diagnostic methods, medical and surgical therapy, the mortality due to undiagnosed Marfan syndrome is still high. The present article reviews the molecular genetic studies of Marfan syndrome since the discovery of the mutations in the fibrillin-1 gene.

  14. Phenotype, Cancer Risk, and Surveillance in Beckwith-Wiedemann Syndrome Depending on Molecular Genetic Subgroups

    NARCIS (Netherlands)

    Maas, Saskia M.; Vansenne, Fleur; Kadouch, Daniel J. M.; Ibrahim, Abdulla; Bliek, Jet; Hopman, Saskia; Mannens, Marcel M.; Merks, Johannes H. M.; Maher, Eamonn R.; Hennekam, Raoul C.

    Patients with Beckwith-Wiedemann syndrome (BWS) have an increased risk to develop cancer in childhood, especially Wilms tumor and hepatoblastoma. The risk varies depending on the cause of BWS. We obtained clinical and molecular data in our cohort of children with BWS, including tumor occurrences,

  15. Molecular genetics

    International Nuclear Information System (INIS)

    Kubitschek, H.E.

    1975-01-01

    Progress is reported on studies on the nature and action of lethal and mutagenic lesions in DNA and the mechanisms by which these are produced in bacteria by ionizing radiation or by decay of radioisotopes incorporated in DNA. Studies of radioisotope decay provide the advantages that the original lesion is localized in the genetic material and the immediate physical and chemical changes that occur at decay are known. Specific types of DNA damage were related to characteristic decay properties of several radioisotopes. Incorporated 125 I, for example, induces a double-stranded break in DNA with almost every decay, but causes remarkably little damage of any other kind to the DNA. (U.S.)

  16. Narcolepsy and familial advanced sleep-phase syndrome: molecular genetics of sleep disorders.

    NARCIS (Netherlands)

    Tafti, M.; Dauvilliers, Y.; Overeem, S.

    2007-01-01

    Sleep disorders are very prevalent and represent an emerging worldwide epidemic. However, research into the molecular genetics of sleep disorders remains surprisingly one of the least active fields. Nevertheless, rapid progress is being made in several prototypical disorders, leading recently to the

  17. Molecular genetics and clinical features of Birt-Hogg-Dubé syndrome.

    Science.gov (United States)

    Schmidt, Laura S; Linehan, W Marston

    2015-10-01

    Birt-Hogg-Dubé (BHD) syndrome is an inherited renal cancer syndrome in which affected individuals are at risk of developing benign cutaneous fibrofolliculomas, bilateral pulmonary cysts and spontaneous pneumothoraces, and kidney tumours. Bilateral multifocal renal tumours that develop in BHD syndrome are most frequently hybrid oncocytic tumours and chromophobe renal carcinoma, but can present with other histologies. Germline mutations in the FLCN gene on chromosome 17 are responsible for BHD syndrome--BHD-associated renal tumours display inactivation of the wild-type FLCN allele by somatic mutation or chromosomal loss, confirming that FLCN is a tumour suppressor gene that fits the classic two-hit model. FLCN interacts with two novel proteins, FNIP1 and FNIP2, and with AMPK, a negative regulator of mTOR. Studies with FLCN-deficient cell and animal models support a role for FLCN in modulating the AKT-mTOR pathway. Emerging evidence links FLCN with a number of other molecular pathways and cellular processes important for cell homeostasis that are frequently deregulated in cancer, including regulation of TFE3 and/or TFEB transcriptional activity, amino-acid-dependent mTOR activation through Rag GTPases, TGFβ signalling, PGC1α-driven mitochondrial biogenesis, and autophagy. Currently, surgical intervention is the only therapy available for BHD-associated renal tumours, but improved understanding of the FLCN pathway will hopefully lead to the development of effective forms of targeted systemic therapy for this disease.

  18. Clinical features and molecular genetic analysis of a boy with Prader-Willi syndrome caused by an imprinting defect

    DEFF Research Database (Denmark)

    Schulze, A; Hansen, Claus; Baekgaard, P

    1997-01-01

    Prader-Willi syndrome (PWS) is a neuroendocrine disorder caused by a non-functioning paternally derived gene(s) within the chromosome region 15q11-q13. Most cases result from microscopically visible deletions of paternal origin, or maternal uniparental disomy of chromosome 15. In both instances...... no recurrence has been reported. In rare cases, PWS is associated with lack of gene expression from the paternal allele due to an imprinting defect. We report the clinical features and the molecular genetic analysis of the first Danish child with PWS due to a defect of the putative imprinting centre (IC). When...

  19. [Molecular genetics of beta-galactosidase deficiency (GM1-gangliosidosis and Morquio syndrome type B)].

    Science.gov (United States)

    Yoshida, K; Yanagisawa, N

    1993-09-01

    Recent advances in the molecular study of beta-galactosidase deficiency (GM1-gangliosidosis and Morquio syndrome type B) are reviewed. Until now, 14 different mutations have been found in the beta-galactosidase gene in patients with this disorder. Gene mutations are heterogeneous, but common and specific mutations have been identified for three types of protracted clinical course; 51Ile-->Thr mutation for Japanese adult/chronic GM1-gangliosidosis, 201Arg-->Cys for Japanese late infantile/juvenile GM1-gangliosidosis and 273Trp-->Leu for Caucasian Morquio syndrome type B. These phenotype-specific mutant genes produce mutant proteins with significant residual enzyme activity, whereas mutant proteins associated with infantile GM1-gangliosidosis patients show complete loss of enzyme activity. The phenotypic variations of this disorder may be related to different mode of intracellular processing and turnover of mutant enzyme proteins.

  20. Incidence, Phenotypic Features and Molecular Genetics of Kallmann Syndrome in Finland

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    Tommiska Johanna

    2011-06-01

    Full Text Available Abstract Background Kallmann syndrome (KS, comprised of congenital hypogonadotropic hypogonadism (HH and anosmia, is a clinically and genetically heterogeneous disorder. Its exact incidence is currently unknown, and a mutation in one of the identified KS genes has only been found in ~30% of the patients. Methods Herein, we investigated epidemiological, clinical, and genetic features of KS in Finland. Results The minimal incidence estimate of KS in Finland was 1:48 000, with clear difference between males (1:30 000 and females (1:125 000 (p = 0.02. The reproductive phenotype of 30 probands (25 men; 5 women ranged from severe HH to partial puberty. Comprehensive mutation analysis of all 7 known KS genes (KAL1, FGFR1, FGF8, PROK2, PROKR2, CHD7, and WDR11 in these 30 well-phenotyped probands revealed mutations in KAL1 (3 men and FGFR1 (all 5 women vs. 4/25 men, but not in other genes. Conclusions Our results suggest that Finnish KS men harbor mutations in gene(s yet-to-be discovered with sex-dependent penetrance of the disease phenotype. In addition, some KS patients without CHD7 mutations display CHARGE-syndrome associated phenotypic features (e.g. ear or eye anomalies, possibly implying that, in addition to CHD7, there may be other genes associated with phenotypes ranging from KS to CHARGE.

  1. Fragile X Syndrome: Keys to the Molecular Genetics of Synaptic Plasticity

    Science.gov (United States)

    Lombroso, Paul J.; Ogren, Marilee P.

    2008-01-01

    Fragile X syndrome, the most common form of inherited mental retardation is discussed. The relationship between specific impairments in synaptic plasticity and Fragile X syndrome is investigated as it strengthens synaptic contacts between neurons.

  2. Molecular Population Genetics.

    Science.gov (United States)

    Casillas, Sònia; Barbadilla, Antonio

    2017-03-01

    Molecular population genetics aims to explain genetic variation and molecular evolution from population genetics principles. The field was born 50 years ago with the first measures of genetic variation in allozyme loci, continued with the nucleotide sequencing era, and is currently in the era of population genomics. During this period, molecular population genetics has been revolutionized by progress in data acquisition and theoretical developments. The conceptual elegance of the neutral theory of molecular evolution or the footprint carved by natural selection on the patterns of genetic variation are two examples of the vast number of inspiring findings of population genetics research. Since the inception of the field, Drosophila has been the prominent model species: molecular variation in populations was first described in Drosophila and most of the population genetics hypotheses were tested in Drosophila species. In this review, we describe the main concepts, methods, and landmarks of molecular population genetics, using the Drosophila model as a reference. We describe the different genetic data sets made available by advances in molecular technologies, and the theoretical developments fostered by these data. Finally, we review the results and new insights provided by the population genomics approach, and conclude by enumerating challenges and new lines of inquiry posed by increasingly large population scale sequence data. Copyright © 2017 Casillas and Barbadilla.

  3. Molecular Population Genetics

    Science.gov (United States)

    Casillas, Sònia; Barbadilla, Antonio

    2017-01-01

    Molecular population genetics aims to explain genetic variation and molecular evolution from population genetics principles. The field was born 50 years ago with the first measures of genetic variation in allozyme loci, continued with the nucleotide sequencing era, and is currently in the era of population genomics. During this period, molecular population genetics has been revolutionized by progress in data acquisition and theoretical developments. The conceptual elegance of the neutral theory of molecular evolution or the footprint carved by natural selection on the patterns of genetic variation are two examples of the vast number of inspiring findings of population genetics research. Since the inception of the field, Drosophila has been the prominent model species: molecular variation in populations was first described in Drosophila and most of the population genetics hypotheses were tested in Drosophila species. In this review, we describe the main concepts, methods, and landmarks of molecular population genetics, using the Drosophila model as a reference. We describe the different genetic data sets made available by advances in molecular technologies, and the theoretical developments fostered by these data. Finally, we review the results and new insights provided by the population genomics approach, and conclude by enumerating challenges and new lines of inquiry posed by increasingly large population scale sequence data. PMID:28270526

  4. Spectrum of novel mutations found in Waardenburg syndrome types 1 and 2: implications for molecular genetic diagnostics

    Science.gov (United States)

    Wildhardt, Gabriele; Zirn, Birgit; Graul-Neumann, Luitgard M; Wechtenbruch, Juliane; Suckfüll, Markus; Buske, Annegret; Bohring, Axel; Kubisch, Christian; Vogt, Stefanie; Strobl-Wildemann, Gertrud; Greally, Marie; Bartsch, Oliver; Steinberger, Daniela

    2013-01-01

    Objectives Till date, mutations in the genes PAX3 and MITF have been described in Waardenburg syndrome (WS), which is clinically characterised by congenital hearing loss and pigmentation anomalies. Our study intended to determine the frequency of mutations and deletions in these genes, to assess the clinical phenotype in detail and to identify rational priorities for molecular genetic diagnostics procedures. Design Prospective analysis. Patients 19 Caucasian patients with typical features of WS underwent stepwise investigation of PAX3 and MITF. When point mutations and small insertions/deletions were excluded by direct sequencing, copy number analysis by multiplex ligation-dependent probe amplification was performed to detect larger deletions and duplications. Clinical data and photographs were collected to facilitate genotype–phenotype analyses. Setting All analyses were performed in a large German laboratory specialised in genetic diagnostics. Results 15 novel and 4 previously published heterozygous mutations in PAX3 and MITF were identified. Of these, six were large deletions or duplications that were only detectable by copy number analysis. All patients with PAX3 mutations had typical phenotype of WS with dystopia canthorum (WS1), whereas patients with MITF gene mutations presented without dystopia canthorum (WS2). In addition, one patient with bilateral hearing loss and blue eyes with iris stroma dysplasia had a de novo missense mutation (p.Arg217Ile) in MITF. MITF 3-bp deletions at amino acid position 217 have previously been described in patients with Tietz syndrome (TS), a clinical entity with hearing loss and generalised hypopigmentation. Conclusions On the basis of these findings, we conclude that sequencing and copy number analysis of both PAX3 and MITF have to be recommended in the routine molecular diagnostic setting for patients, WS1 and WS2. Furthermore, our genotype–phenotype analyses indicate that WS2 and TS correspond to a clinical spectrum

  5. Pendred syndrome in two Galician families: insights into clinical phenotypes through cellular, genetic, and molecular studies.

    Science.gov (United States)

    Palos, Fernando; García-Rendueles, María E R; Araujo-Vilar, David; Obregon, Maria Jesús; Calvo, Rosa Maria; Cameselle-Teijeiro, Jose; Bravo, Susana B; Perez-Guerra, Oscar; Loidi, Lourdes; Czarnocka, Barbara; Alvarez, Paula; Refetoff, Samuel; Dominguez-Gerpe, Lourdes; Alvarez, Clara V; Lado-Abeal, Joaquin

    2008-01-01

    We studied two families from Galicia (northwest Spain) with Pendred syndrome (PS) and unusual thyroid phenotypes. In family A, the proposita had a large goiter and hypothyroxinemia but normal TSH and free T3 (FT3). In family B, some affected members showed deafness but not goiter. Our objective was to identify the mutations causing PS and molecular mechanisms underlying the thyroid phenotypes. Interventions included extraction of DNA and of thyroid tissue. Propositi and 10 members of the two families participated in the study. Main outcome measures included SLC26A4 gene analysis, deiodinase activities in thyroid tissue, and c.416-1G-->A effects on SLC26A4 splicing. In addition, a primary PS thyrocyte culture, T-PS2, was obtained from propositus B and compared with another culture of normal human thyrocytes, NT, by Western blotting, confocal microscopy, and iodine uptake kinetics. Proposita A was heterozygous for c.578C-->T and c.279delT, presented with goiter, and had normal TSH and FT3 but low FT4 attributable to high type 1 and type 2 iodothyronine deiodinase activities in the goiter. Propositus B bore c.279delT and a novel mutation c.416-1G-->A; some deaf relatives were homozygous for c.416-1G-->A but did not present goiter. The c.279delT mutation was associated with identical haplotype in the two families. T-PS2 showed truncated pendrin retained intracellularly and high iodine uptake with low efflux leading to iodine retention. c.279delT is a founder mutation in Galicia. Proposita A adapted to poor organification by increasing deiodinase activities in the goiter, avoiding hypothyroidism. Lack of goiter in subjects homozygous for c.416-1G-->A was due to incomplete penetrance allowing synthesis of some wild-type pendrin. Intracellular iodine retention, as seen in T-PS2, could play a role in thyroid alterations in PS.

  6. Genetics Home Reference: DOORS syndrome

    Science.gov (United States)

    ... This Page Campeau PM, Hennekam RC; DOORS syndrome collaborative group. DOORS syndrome: phenotype, genotype and comparison with ... M. DOOR syndrome: clinical report, literature review and discussion of natural history. Am J Med Genet A. ...

  7. Genetics Home Reference: Waardenburg syndrome

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions Waardenburg syndrome Waardenburg syndrome Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Waardenburg syndrome is a group of genetic conditions that can ...

  8. Molecular genetics in aquaculture

    Directory of Open Access Journals (Sweden)

    Liliana Di Stasio

    2010-01-01

    Full Text Available Great advances in molecular genetics have deeply changed the way of doing research in aquaculture, as it has already done in other fields. The molecular revolution started in the 1980’s, thanks to the widespread use of restriction enzymes and Polymerase Chain Reaction technology, which makes it possible to easily detect the genetic variability directly at the DNA level. In aquaculture, the molecular data are used for several purposes, which can be clustered into two main groups. The first one, focused on individuals, includes the sex identification and parentage assignment, while the second one, focused on populations, includes the wide area of the genetic characterization, aimed at solving taxonomic uncertainties, preserving genetic biodiversity and detecting genetic tags. For the future, the increase in the number of molecular markers and the construction of high density genetic maps, as well as the implementation of genomic resources (including genome sequencing, are expected to provide tools for the genetic improvement of aquaculture species through Marked Assisted Selection. In this review the characteristics of different types of molecular markers, along with their applications to a variety of aquaculture issues are presented.

  9. Genetics Home Reference: arterial tortuosity syndrome

    Science.gov (United States)

    ... Barrow M, Dekens R, Loeys BL, Coucke PJ, De Paepe AM. Arterial tortuosity syndrome: clinical and molecular findings in 12 newly identified ... R, Dietz HC, Barlati S, Colombi M, Loeys B, De Paepe A. Mutations in the ... and cause arterial tortuosity syndrome. Nat Genet. 2006 Apr;38(4):452-7. ...

  10. Scientific Statement on the Diagnostic Criteria, Epidemiology, Pathophysiology, and Molecular Genetics of Polycystic Ovary Syndrome

    Science.gov (United States)

    Dumesic, Daniel A.; Oberfield, Sharon E.; Stener-Victorin, Elisabet; Marshall, John C.; Laven, Joop S.

    2015-01-01

    Polycystic ovary syndrome (PCOS) is a heterogeneous and complex disorder that has both adverse reproductive and metabolic implications for affected women. However, there is generally poor understanding of its etiology. Varying expert-based diagnostic criteria utilize some combination of oligo-ovulation, hyperandrogenism, and the presence of polycystic ovaries. Criteria that require hyperandrogenism tend to identify a more severe reproductive and metabolic phenotype. The phenotype can vary by race and ethnicity, is difficult to define in the perimenarchal and perimenopausal period, and is exacerbated by obesity. The pathophysiology involves abnormal gonadotropin secretion from a reduced hypothalamic feedback response to circulating sex steroids, altered ovarian morphology and functional changes, and disordered insulin action in a variety of target tissues. PCOS clusters in families and both female and male relatives can show stigmata of the syndrome, including metabolic abnormalities. Genome-wide association studies have identified a number of candidate regions, although their role in contributing to PCOS is still largely unknown. PMID:26426951

  11. Genetic syndromes associated with overgrowth in childhood

    Directory of Open Access Journals (Sweden)

    Jung Min Ko

    2013-09-01

    Full Text Available Overgrowth syndromes comprise a diverse group of conditions with unique clinical, behavioral and molecular genetic features. While considerable overlap in presentation sometimes exists, advances in identification of the precise etiology of specific overgrowth disorders continue to improve clinicians' ability to make an accurate diagnosis. Among them, this paper introduces two classic genetic overgrowth syndromes: Sotos syndrome and Beckwith-Wiedemann syndrome. Historically, the diagnosis was based entirely on clinical findings. However, it is now understood that Sotos syndrome is caused by a variety of molecular genetic alterations resulting in haploinsufficiency of the NSD1 gene at chromosome 5q35 and that Beckwith-Wiedemann syndrome is caused by heterogeneous abnormalities in the imprinting of a number of growth regulatory genes within chromosome 11p15 in the majority of cases. Interestingly, the 11p15 imprinting region is also associated with Russell-Silver syndrome which is a typical growth retardation syndrome. Opposite epigenetic alterations in 11p15 result in opposite clinical features shown in Beckwith-Wiedemann syndrome and Russell-Silver syndrome. Although the exact functions of the causing genes have not yet been completely understood, these overgrowth syndromes can be good models to clarify the complex basis of human growth and help to develop better-directed therapies in the future.

  12. Molecular-genetic diagnostics of von Hippel-Lindau syndrome (VHL) in Bulgaria: first complex mutation event in the VHL gene.

    Science.gov (United States)

    Glushkova, Maria; Dimova, Petia; Yordanova, Iglika; Todorov, Tihomir; Tourtourikov, Ivan; Mitev, Vanyo; Todorova, Albena

    2018-02-01

    Von Hippel-Lindau syndrome is an autosomal-dominant disease characterized by the formation of various tumours and cysts in many different parts of the body. Von Hippel-Lindau syndrome is caused by VHL gene mutations leading to production of impaired tumor suppressor Von Hippel-Lindau syndrome protein or its complete absence. To study five patients with clinically suspected Von Hippel-Lindau syndrome, who were referred for molecular genetic testing. Sanger sequencing of the coding regions of the VHL gene. Five clinically relevant germline mutations were detected. One of the pathogenic variants has not been previously reported. This novel mutation is a complex mutation event combining a duplication and an indel, rearranging exon 3 of the VHL gene - c. [516_517dupGTCAAGCCT; 532_542delCTGGACATCGTinsATTA], p. (Glu173Serfs*4). Overall, our results showed that the diagnosis of Von Hippel-Lindau syndrome in our country is difficult most probably because of its heterogeneous clinical manifestation and insufficient knowledge on the diagnostic criteria for the disease. From genetic point of view our results add some novel data on the mutation profile of the VHL gene. In order to prove or revise the diagnosis, early genetic testing is strongly recommended in affected patients and their family members to ensure appropriate follow-up and treatment of the malignancies.

  13. Primer on molecular genetics

    Energy Technology Data Exchange (ETDEWEB)

    1992-04-01

    This report is taken from the April 1992 draft of the DOE Human Genome 1991--1992 Program Report, which is expected to be published in May 1992. The primer is intended to be an introduction to basic principles of molecular genetics pertaining to the genome project. The material contained herein is not final and may be incomplete. Techniques of genetic mapping and DNA sequencing are described.

  14. Molecular genetic analysis of individuals with Williams syndrome and supravalvar aortic stenosis

    Energy Technology Data Exchange (ETDEWEB)

    Smoot, L.B.; Lacro, R.V.; Kunkel, L.M. [Children`s Hospital, Boston, MA (United States); Pober, B. [Yale Univ., New Haven, CT (United States)

    1994-09-01

    Mutations at the elastin locus (chromosome 7q11.23) have been demonstrated in individuals with Williams syndrome (WS) and familial supravalvar aortic stenosis (SVAS). Relationships between elastin mutations and vascular and/or neurodevelopmental pathology have yet to be defined. In determining phenotype-genotype correlations in WS/SVAS, we examined 35 individuals with sporadic WS, families with SVAS affecting multiple members, and sporadic cases of isolated obstructive vascular disease. Full length elastin cDNA was used to probe a human genomic library from which multiple elastin genomic clones have been isolated and ordered relative to the elastin gene, covering a minimum of 35 kb. (Additional genomic clones are being obtained by {open_quote}walking{close_quote} 5{prime} and 3{prime} to elastin.) Elastin genomic clones were used as probes in fluorescent in situ hybridization of metaphase chromosomes from WS/SVAS patients. Preliminary analysis confirms elastin deletions in WS patients, but have not yet been demonstrated in patients with isolated vascular disease using this technique. Results of deletional analysis in individuals representing a wide spectrum of phenotypes will be presented.

  15. Genetics Home Reference: Kuskokwim syndrome

    Science.gov (United States)

    ... region of southwest Alaska known as the Kuskokwim River Delta. In Kuskokwim syndrome , contractures most commonly affect ... syndrome 1 General Information from MedlinePlus (5 links) Diagnostic Tests Drug Therapy Genetic Counseling Palliative Care Surgery ...

  16. Genetics Home Reference: Donohue syndrome

    Science.gov (United States)

    ... Genetic Testing Registry: Leprechaunism syndrome Other Diagnosis and Management Resources (1 link) GeneReview: INSR-Related Severe Syndromic Insulin Resistance General Information from MedlinePlus (5 links) Diagnostic Tests ...

  17. Genetics Home Reference: RAPADILINO syndrome

    Science.gov (United States)

    ... navigation Home Page Search Home Health Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Share: Email ... Rapadilino syndrome Hospital for Sick Children: Radial Ray Anomaly MalaCards: rapadilino syndrome March of Dimes: Cleft Lip ...

  18. Molecular aspects of Down syndrome.

    Science.gov (United States)

    Dutta, Samikshan; Nandagopal, Krishnadas; Gangopadhyay, Prasanta Kumar; Mukhopadhyay, Kanchan

    2005-04-01

    Molecular aspects of Down syndrome (DS), a major genetic cause for mental retardation, commonly associated with trisomy 21 are discussed. Two different hypotheses have been speculated to better understand the disease. One believes that increased gene dosage contributes to the phenotypic abnormalities; the other correlates genetic imbalance with DS pathogenesis. To sustain these hypotheses, different murine models have been developed. Experimental models as well as sequencing of human chromosome 21 helped in speculating a few possible candidate genes for DS. However, the phenotypic changes involved with this neurological disorder vis-a-vis the enhanced number of genes, still remain unexplained. Improvement in screening pattern, model system, as well as better understanding of the disease etiology may help in developing efficacious therapeutic regimes for DS.

  19. Genetics Home Reference: Williams syndrome

    Science.gov (United States)

    ... CA, Berman KF. Neural correlates of genetically abnormal social cognition in Williams syndrome. Nat Neurosci. 2005 Aug;8(8):991-3. Epub 2005 Jul 10. Citation on PubMed Meyer-Lindenberg A, Mervis CB, Berman KF. Neural mechanisms in Williams syndrome: a unique window to genetic ...

  20. Genetics Home Reference: Griscelli syndrome

    Science.gov (United States)

    ... Tezcan I, Ersoy F, Houdusse A, Fischer A, de Saint Basile G. Griscelli syndrome restricted to hypopigmentation results from a melanophilin defect ( ... N, Bianchi D, Fischer A, Le Deist F, de Saint Basile G. Mutations in RAB27A ... syndrome associated with haemophagocytic syndrome. Nat Genet. 2000 Jun; ...

  1. Medulloblastoma: Molecular Genetics and Animal Models

    Directory of Open Access Journals (Sweden)

    Corey Raffel

    2004-07-01

    Full Text Available Medulloblastoma is a primary brain tumor found in the cerebellum of children. The tumor occurs in association with two inherited cancer syndromes: Turcot syndrome and Gorlin syndrome. Insights into the molecular biology of the tumor have come from looking at alterations in the genes altered in these syndromes, PTC and APC, respectively. Murine models of medulloblastoma have been constructed based on these alterations. Additional murine models that, while mimicking the appearance of the human tumor, seem unrelated to the human tumor's molecular alterations have been made. In this review, the clinical picture, origin, molecular biology, murine models of medulloblastoma are discussed. Although a great deal has been discovered about this tumor, the genetic alterations responsible for tumor development in a majority of patients have yet to be described.

  2. X-linked hyper-immunoglobulin M syndrome: molecular genetic study and long-time follow-up of three generations of a Chinese family.

    Science.gov (United States)

    Lin, Sheng-Chieh; Shyur, Shyh-Dar; Lee, Wen-I; Ma, Yi-Chun; Huang, Li-Hsin

    2006-01-01

    X-linked hyper-immunoglobulin M (IgM) syndrome (XHIGM) is a rare immunodeficiency disease caused by mutations of the CD40 ligand gene. Patients are subject to recurrent infections and have normal or elevated levels of IgM but markedly decreased serum IgG. We describe molecular genetic studies and clinical manifestations in three generations of one family, as well as results of long-term treatment of 2 young men with the disorder. Of 37 living family members, mutational analysis of the CD40 ligand gene was performed in 36 members. Laboratory data for patients and carriers were reviewed. Four male family members had died of unexplained causes. The 3 patients with XHIGM syndrome and the 5 carriers all had a novel mutation located at Tyr 169 Asn (T526A) in exon 5, the tumor necrosis factor domain of the CD40 ligand gene. In the 3 patients, CD40 ligand expression in activated CD4+ T cells was below 1%. In the carriers, about half of activated CD4+ cells expressed CD40 ligand. One carrier had malignant lymphoma. Long-term (>20 years) intravenous immunoglobulin therapy in 2 patients improved IgG levels but did not fully suppress the high levels of IgM, nor did it prevent late complications (bronchiectasis and sclerosing cholangitis). Diagnosis of a genetic immunodeficiency, especially an X-linked disease such as XHIGM syndrome, should prompt a survey of the entire family. Copyright 2006 S. Karger AG, Basel.

  3. Molecular genetic medicine. Vol. 2

    Energy Technology Data Exchange (ETDEWEB)

    Friedmann, T. (ed.)

    1992-01-01

    Theodore Friedmann has put together an interesting spectrum of articles for volume 2 of Molecular Genetic Medicine. Perhaps related to his own interest in the X chromosome, three articles deal with X-chromosomal topics, while two deal with autosomal disorders and two treat viral disorders. The fragile-X syndrome is thoroughly covered by Brown and Jenkins with an article that is heavily weighted to clinical aspects and now out-of-date RFLP approaches. The timeliness of the volume is insured by the coverage (albeit brief) that they give to the cloning of FMR-1. Gartler et al. present a balanced review of X inactivation - the oft-surveyed subject was comprehensively covered in a manner that provided new perspectives. Lambert et al. provide an exhaustive review of natural and induced mutation of hypoxanthine phosphoribosyltransferase. For autosomal disorders, an excellent review of the molecular genetics of hemoglobin syntheses and their alterations in disease is provided by Berg and Schecter. The level of detail presented seemed just right to this reviewer. A concise review of recent advances in the study of Down syndrome and its animal model, trisomy 16 mice, is provided by Holtzman and Epstein. With regard to viral topics, Chisari thoughtfully reviews hepatitis B virus structure and function and the possible pathogenic mechanisms involved in its induction of hepatocellular carcinoma. Wong-Staal and Haseltine's up-to-date review of the increasingly complex regulatory genes of HIV is marred by a mix-up in figure legends - an exception to an otherwise well-proofread book. In summary, this is a good volume of its type and is recommended for those who might benefit from reading such review articles.

  4. Genetics Home Reference: Shprintzen-Goldberg syndrome

    Science.gov (United States)

    ... those of people with a genetic condition called Marfan syndrome . For example, they may have long, slender fingers ( ... has signs and symptoms similar to those of Marfan syndrome and another genetic condition called Loeys-Dietz syndrome . ...

  5. Genetics Home Reference: FG syndrome

    Science.gov (United States)

    ... genetic condition that affects many parts of the body and occurs almost exclusively in males. "FG" represents the surname initials of the first family diagnosed with the disorder. FG syndrome affects intelligence and behavior. Almost everyone with the condition has ...

  6. Genetics Home Reference: Omenn syndrome

    Science.gov (United States)

    ... Immunodeficiency Disorders Health Topic: Immune System and Disorders Genetic and Rare Diseases Information Center (1 link) Omenn syndrome Additional NIH Resources (1 link) National Institute of Allergy and Infectious Diseases: Primary Immune Deficiency Diseases Educational Resources (8 ...

  7. Cardiac channelopathies: genetic and molecular mechanisms.

    Science.gov (United States)

    Abriel, Hugues; Zaklyazminskaya, Elena V

    2013-03-15

    Channelopathies are diseases caused by dysfunctional ion channels, due to either genetic or acquired pathological factors. Inherited cardiac arrhythmic syndromes are among the most studied human disorders involving ion channels. Since seminal observations made in 1995, thousands of mutations have been found in many of the different genes that code for cardiac ion channel subunits and proteins that regulate the cardiac ion channels. The main phenotypes observed in patients carrying these mutations are congenital long QT syndrome (LQTS), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), short QT syndrome (SQTS) and variable types of conduction defects (CD). The goal of this review is to present an update of the main genetic and molecular mechanisms, as well as the associated phenotypes of cardiac channelopathies as of 2012. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Molecular Biology of Exfoliation Syndrome.

    Science.gov (United States)

    Schlötzer-Schrehardt, Ursula

    2018-02-06

    Exfoliation syndrome (XFS) is a common age-related matrix process resulting from excessive production and disordered assembly of elastic microfibrillar components into highly cross-linked fibrillary aggregates throughout the anterior eye segment and various organ systems. The underlying molecular pathophysiology involves a complex interplay of pro-fibrotic protagonists including growth factors, proteolytic enzymes and inhibitors, pro-inflammatory cytokines, chaperones, and dysregulated stress response pathways including insufficient autophagy. Interaction between individual genetic predisposition and stress factors is a plausible theory explaining the development of XFS in the aging individual. Genome-wide association studies have identified robust genetic associations with LOXL1, CACNA1A, and five additional genes including POMP and TMEM136, which provide new biological insights into the pathology of XFS and highlight a role for abnormal matrix cross-linking processes, Ca channel deficiency, blood-aqueous barrier dysfunction, and abnormal ubiquitin-proteasome signaling in XFS pathophysiology. However, the exact pathophysiological mechanisms, the functional role of genetic risk variants and gene-environmental interactions still remain to be characterized.

  9. Clinical features and molecular genetic analysis of a boy with Prader-Willi syndrome caused by an imprinting defect

    DEFF Research Database (Denmark)

    Schulze, A; Hansen, Claus; Baekgaard, P

    1997-01-01

    no recurrence has been reported. In rare cases, PWS is associated with lack of gene expression from the paternal allele due to an imprinting defect. We report the clinical features and the molecular genetic analysis of the first Danish child with PWS due to a defect of the putative imprinting centre (IC). When...... the imprinting mutation is inherited from a carrier father, the risk that future children will be affected is theoretically 50%. It is therefore important that these families are referred to a geneticist for counselling and further investigation. Prenatal diagnosis is currently only feasible when the mutation...

  10. Genetics Home Reference: ADNP syndrome

    Science.gov (United States)

    ... der Aa N. A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP. Nat Genet. 2014 Apr;46(4):380-4. doi: 10.1038/ng.2899. Citation on PubMed or ... of Helsmoortel-Van der Aa syndrome associated with a novel truncating mutation in ADNP ...

  11. Genetics Home Reference: acrocallosal syndrome

    Science.gov (United States)

    ... E, Perveen R, Donnai D, Wall S, Black GC. De novo GLI3 mutation in acrocallosal syndrome: broadening the phenotypic spectrum of GLI3 defects and ... C, Biesecker LG, Willems PJ, Wessels MW. A de novo GLI3 mutation in a patient with acrocallosal syndrome. Am J Med Genet A. 2013 Jun;161A( ...

  12. Changes in the folding landscape of the WW domain provide a molecular mechanism for an inherited genetic syndrome

    Science.gov (United States)

    Pucheta-Martinez, Encarna; D'Amelio, Nicola; Lelli, Moreno; Martinez-Torrecuadrada, Jorge L.; Sudol, Marius; Saladino, Giorgio; Gervasio, Francesco Luigi

    2016-07-01

    WW domains are small domains present in many human proteins with a wide array of functions and acting through the recognition of proline-rich sequences. The WW domain belonging to polyglutamine tract-binding protein 1 (PQBP1) is of particular interest due to its direct involvement in several X chromosome-linked intellectual disabilities, including Golabi-Ito-Hall (GIH) syndrome, where a single point mutation (Y65C) correlates with the development of the disease. The mutant cannot bind to its natural ligand WBP11, which regulates mRNA processing. In this work we use high-field high-resolution NMR and enhanced sampling molecular dynamics simulations to gain insight into the molecular causes the disease. We find that the wild type protein is partially unfolded exchanging among multiple beta-strand-like conformations in solution. The Y65C mutation further destabilizes the residual fold and primes the protein for the formation of a disulphide bridge, which could be at the origin of the loss of function.

  13. EMQN best practice guidelines for the molecular genetic testing and reporting of fragile X syndrome and other fragile X-associated disorders.

    Science.gov (United States)

    Biancalana, Valérie; Glaeser, Dieter; McQuaid, Shirley; Steinbach, Peter

    2015-04-01

    Different mutations occurring in the unstable CGG repeat in 5' untranslated region of FMR1 gene are responsible for three fragile X-associated disorders. An expansion of over ∼200 CGG repeats when associated with abnormal methylation and inactivation of the promoter is the mutation termed 'full mutation' and is responsible for fragile X syndrome (FXS), a neurodevelopmental disorder described as the most common cause of inherited intellectual impairment. The term 'abnormal methylation' is used here to distinguish the DNA methylation induced by the expanded repeat from the 'normal methylation' occurring on the inactive X chromosomes in females with normal, premutation, and full mutation alleles. All male and roughly half of the female full mutation carriers have FXS. Another anomaly termed 'premutation' is characterized by the presence of 55 to ∼200 CGGs without abnormal methylation, and is the cause of two other diseases with incomplete penetrance. One is fragile X-associated primary ovarian insufficiency (FXPOI), which is characterized by a large spectrum of ovarian dysfunction phenotypes and possible early menopause as the end stage. The other is fragile X-associated tremor/ataxia syndrome (FXTAS), which is a late onset neurodegenerative disorder affecting males and females. Because of the particular pattern and transmission of the CGG repeat, appropriate molecular testing and reporting is very important for the optimal genetic counselling in the three fragile X-associated disorders. Here, we describe best practice guidelines for genetic analysis and reporting in FXS, FXPOI, and FXTAS, including carrier and prenatal testing.

  14. Molecular and Clinical Aspects of Angelman Syndrome

    Science.gov (United States)

    Dagli, A.; Buiting, K.; Williams, C.A.

    2012-01-01

    The Angelman syndrome is caused by disruption of the UBE3A gene and is clinically delineated by the combination of severe mental disability, seizures, absent speech, hypermotoric and ataxic movements, and certain remarkable behaviors. Those with the syndrome have a predisposition toward apparent happiness and paroxysms of laughter, and this finding helps distinguish Angelman syndrome from other conditions involving severe developmental handicap. Accurate diagnosis rests on a combination of clinical criteria and molecular and/or cytogenetic testing. Analysis of parent-specific DNA methylation imprints in the critical 15q11.2–q13 genomic region identifies 75–80% of all individuals with the syndrome, including those with cytogenetic deletions, imprinting center defects and paternal uniparental disomy. In the remaining group, UBE3A sequence analysis identifies an additional percentage of patients, but 5–10% will remain who appear to have the major clinical phenotypic features but do not have any identifiable genetic abnormalities. Genetic counseling for recurrence risk is complicated because multiple genetic mechanisms can disrupt the UBE3A gene, and there is also a unique inheritance pattern associated with UBE3A imprinting. Angelman syndrome is a prototypical developmental syndrome due to its remarkable behavioral phenotype and because UBE3A is so crucial to normal synaptic function and neural plasticity. PMID:22670133

  15. Down Syndrome - Genetics and Cardiogenetics.

    Science.gov (United States)

    Plaiasu, Vasilica

    2017-09-01

    During the last years, Down syndrome has been the focus of special attention. Down syndrome is a genetic disorder characterized by distinct physical features and some degree of cognitive disability. Patients with Down syndrome also present many other congenital anomalies. The mapping for phenotypes to specific regions of chromosome 21 permits to identify which genes (or small regions) contribute to the phenotypic features of Down syndrome and thus, to understand its pathogenesis. Mainly there are three cytogenetic forms of Down syndrome: free trisomy 21, mosaic trisomy 21 and robertsonian translocation trisomy 21. Prenatal and postnatal testing has become commonly used to diagnose different cases presenting the same pathology. Early clinical diagnosis is extremely important for patient prognosis. Lately, advances in Down syndrome research have been registered, but little is known about cardiovascular phenotype in Down syndrome. About half of patients with Down syndrome have congenital heart disease, and atrioventricular septal defects are the most common defects found. Basic research on Down syndrome is now rapidly accelerating, using new genomic technologies. There were many studies performed to identify a correlation between genotype and phenotype in Down syndrome.

  16. Molecular Analysis of Collagen XVIII Reveals Novel Mutations, Presence of a Third Isoform, and Possible Genetic Heterogeneity in Knobloch Syndrome

    Science.gov (United States)

    Suzuki, O. T.; Sertié, A. L.; Der Kaloustian, V. M.; Kok, F.; Carpenter, M.; Murray, J.; Czeizel, A. E.; Kliemann, S. E.; Rosemberg, S.; Monteiro, M.; Olsen, B. R.; Passos-Bueno, M. R.

    2002-01-01

    Knobloch syndrome (KS) is a rare disease characterized by severe ocular alterations, including vitreoretinal degeneration associated with retinal detachment and occipital scalp defect. The responsible gene, COL18A1, has been mapped to 21q22.3, and, on the basis of the analysis of one family, we have demonstrated that a mutation affecting only one of the three COL18A1 isoforms causes this phenotype. We report here the results of the screening of both the entire coding region and the exon-intron boundaries of the COL18A1 gene (which includes 43 exons), in eight unrelated patients with KS. Besides 20 polymorphic changes, we identified 6 different pathogenic changes in both alleles of five unrelated patients with KS (three compound heterozygotes and two homozygotes). All are truncating mutations leading to deficiency of one or all collagen XVIII isoforms and endostatin. We have verified that, in exon 41, the deletion c3514-3515delCT, found in three unrelated alleles, is embedded in different haplotypes, suggesting that this mutation has occurred more than once. In addition, our results provide evidence of nonallelic genetic heterogeneity in KS. We also show that the longest human isoform (NC11-728) is expressed in several tissues (including the human eye) and that lack of either the short variant or all of the collagen XVIII isoforms causes similar phenotypes but that those patients who lack all forms present more-severe ocular alterations. Despite the small sample size, we found low endostatin plasma levels in those patients with mutations leading to deficiency of all isoforms; in addition, it seems that absence of all collagen XVIII isoforms causes predisposition to epilepsy. PMID:12415512

  17. Genetics Home Reference: Denys-Drash syndrome

    Science.gov (United States)

    ... Conditions Diagnosis & Management Resources Genetic Testing (1 link) Genetic Testing Registry: Drash syndrome Other Diagnosis and Management Resources (2 links) GeneReview: Wilms Tumor Predisposition MedlinePlus Encyclopedia: Nephrotic Syndrome General Information from MedlinePlus ( ...

  18. Genetics Home Reference: fragile X syndrome

    Science.gov (United States)

    ... Facebook Twitter Home Health Conditions Fragile X syndrome Fragile X syndrome Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Fragile X syndrome is a genetic condition that causes a ...

  19. Genetics Home Reference: Aarskog-Scott syndrome

    Science.gov (United States)

    ... Twitter Home Health Conditions Aarskog-Scott syndrome Aarskog-Scott syndrome Printable PDF Open All Close All Enable ... to view the expand/collapse boxes. Description Aarskog-Scott syndrome is a genetic disorder that affects the ...

  20. Genetics Home Reference: Hartsfield syndrome

    Science.gov (United States)

    ... Epub 2016 May 12. Citation on PubMed Shi Y, Dhamija R, Wren C, Wang X, Babovic-Vuksanovic D, Spector E. Detection of gonadal mosaicism in Hartsfield syndrome by next generation sequencing. Am J Med Genet A. 2016 Sep ...

  1. EMQN best practice guidelines for the molecular genetic testing and reporting of fragile X syndrome and other fragile X-associated disorders

    Science.gov (United States)

    Biancalana, Valérie; Glaeser, Dieter; McQuaid, Shirley; Steinbach, Peter

    2015-01-01

    Different mutations occurring in the unstable CGG repeat in 5' untranslated region of FMR1 gene are responsible for three fragile X-associated disorders. An expansion of over ∼200 CGG repeats when associated with abnormal methylation and inactivation of the promoter is the mutation termed ‘full mutation' and is responsible for fragile X syndrome (FXS), a neurodevelopmental disorder described as the most common cause of inherited intellectual impairment. The term ‘abnormal methylation' is used here to distinguish the DNA methylation induced by the expanded repeat from the ‘normal methylation' occurring on the inactive X chromosomes in females with normal, premutation, and full mutation alleles. All male and roughly half of the female full mutation carriers have FXS. Another anomaly termed ‘premutation' is characterized by the presence of 55 to ∼200 CGGs without abnormal methylation, and is the cause of two other diseases with incomplete penetrance. One is fragile X-associated primary ovarian insufficiency (FXPOI), which is characterized by a large spectrum of ovarian dysfunction phenotypes and possible early menopause as the end stage. The other is fragile X-associated tremor/ataxia syndrome (FXTAS), which is a late onset neurodegenerative disorder affecting males and females. Because of the particular pattern and transmission of the CGG repeat, appropriate molecular testing and reporting is very important for the optimal genetic counselling in the three fragile X-associated disorders. Here, we describe best practice guidelines for genetic analysis and reporting in FXS, FXPOI, and FXTAS, including carrier and prenatal testing. PMID:25227148

  2. Molecular Genetics of Epilepsy: A Clinician's Perspective.

    Science.gov (United States)

    Dhiman, Vikas

    2017-01-01

    Epilepsy is a common neurological problem, and there is a genetic basis in almost 50% of people with epilepsy. The diagnosis of genetic epilepsies makes the patient assured of the reasons of his/her seizures and avoids unnecessary, expensive, and invasive investigations. Last decade has shown tremendous growth in gene sequencing technologies, which have made genetic tests available at the bedside. Whole exome sequencing is now being routinely used in the clinical setting for making a genetic diagnosis. Genetic testing not only makes the diagnosis but also has an effect on the management of the patients, for example, the role of sodium channels blockers in SCN1A + Dravet syndrome patients and usefulness of ketogenic diet therapy in SLC2A1 + generalized epilepsy patients. Many clinicians in our country have no or limited knowledge about the molecular genetics of epilepsies, types of genetic tests available, how to access them and how to interpret the results. The purpose of this review is to give an overview in this direction and encourage the clinicians to start considering genetic testing as an important investigation along with electroencephalogram and magnetic resonance imaging for better understanding and management of epilepsy in their patients.

  3. Molecular genetics of epilepsy: A clinician's perspective

    Directory of Open Access Journals (Sweden)

    Vikas Dhiman

    2017-01-01

    Full Text Available Epilepsy is a common neurological problem, and there is a genetic basis in almost 50% of people with epilepsy. The diagnosis of genetic epilepsies makes the patient assured of the reasons of his/her seizures and avoids unnecessary, expensive, and invasive investigations. Last decade has shown tremendous growth in gene sequencing technologies, which have made genetic tests available at the bedside. Whole exome sequencing is now being routinely used in the clinical setting for making a genetic diagnosis. Genetic testing not only makes the diagnosis but also has an effect on the management of the patients, for example, the role of sodium channels blockers in SCN1A+ Dravet syndrome patients and usefulness of ketogenic diet therapy in SLC2A1+ generalized epilepsy patients. Many clinicians in our country have no or limited knowledge about the molecular genetics of epilepsies, types of genetic tests available, how to access them and how to interpret the results. The purpose of this review is to give an overview in this direction and encourage the clinicians to start considering genetic testing as an important investigation along with electroencephalogram and magnetic resonance imaging for better understanding and management of epilepsy in their patients.

  4. Molecular Genetics of Analbuminaemia

    DEFF Research Database (Denmark)

    Minchiotti, Lorenzo; Caridi, Gianluca; Campagnoli, Monica

    2014-01-01

    the perinatal and childhood period. Twenty-one different molecular lesions in the ALB are now known as cause of the trait. These include one mutation in the start codon, one frameshift/insertion, five frameshift/deletions, seven nonsense mutations and seven mutations affecting splicing. Thus, nonsense mutations...

  5. Diagnostic criteria for congenital long QT syndrome in the era of molecular genetics: do we need a scoring system?

    NARCIS (Netherlands)

    Hofman, Nynke; Wilde, Arthur A. M.; Kääb, Stefan; van Langen, Irene M.; Tanck, Michael W. T.; Mannens, Marcel M. A. M.; Hinterseer, Martin; Beckmann, Britt-Maria; Tan, Hanno L.

    2007-01-01

    AIMS: Previously published diagnostic systems, based on ECG analysis and clinical parameters (Schwartz criteria and Keating criteria), have been used to estimate the probability of inherited long QT syndrome (LQTS). Nowadays, a certain diagnosis can often be made by DNA testing. We aimed to

  6. Diagnostic criteria for congenital long QT syndrome in the era of molecular genetics: Do we need a scoring system?

    NARCIS (Netherlands)

    Hofman, Nynke; Wilde, Arthur A.M.; Kääb, Stefan; Van Langen, Irene M.; Tanck, Michael W.T.; Mannens, Marcel M.A.M.; Hinterseer, Martin; Beckmann, Britt-Maria; Tan, Hanno L.

    2007-01-01

    Aims: Previously published diagnostic systems, based on ECG analysis and clinical parameters (Schwartz criteria and Keating criteria), have been used to estimate the probability of inherited long QT syndrome (LQTS). Nowadays, a certain diagnosis can often be made by DNA testing. We aimed to

  7. Genetic Aspects of Nephrotic Syndrome

    DEFF Research Database (Denmark)

    Joshi, Shivani

    steroid dependence or become frequent relapsers. Repeated courses of corticosteroid treatment often cause significant associated morbidity. Familial occurrence of SSNS is rare and suggests a potential genetic origin. However, very little data on molecular genetics of familial SSNS is available...... with SSNS are rare, but do indicate a genetic predisposition. In study III we investigated a potential genetic linkage in 9 European SSNS families with at least two affected siblings. Using SNP6 whole genome linkage analysis we could establish linkage of the disease phenotype to chromosome 15 with a maximum...... immunosuppressive treatment in future patients with the same genotype. Our findings also demonstrate that inheritance of different alleles at independent genetic loci in NS may contribute to the disease phenotype. SSNS is clinically distinct from SRNS and its pathogenesis is still unclear. Our study showed linkage...

  8. The genetics of fibromyalgia syndrome.

    Science.gov (United States)

    Buskila, Dan; Sarzi-Puttini, Piercarlo; Ablin, Jacob N

    2007-01-01

    Fibromyalgia syndrome (FMS) is a common chronic widespread pain syndrome mainly affecting women. Although the etiology of FMS is not completely understood, varieties of neuroendocrine disturbances, as well as abnormalities of autonomic function, have been implicated in its pathogenesis. The exposure of a genetically predisposed individual to a host of environmental stressors is presumed to lead to the development of FMS. Fibromyalgia overlaps with several related syndromes, collectively compromising the spectrum of the functional somatic disorder. FMS is characterized by a strong familial aggregation. Recent evidence suggests a role for polymorphisms of genes in the serotoninergic, dopaminergic and catecholaminergic systems in the etiopathogenesis of FMS. These polymorphisms are not specific for FMS and are similarly associated with additional comorbid conditions. The mode of inheritance in FMS is unknown, but it is most probably polygenic. Recognition of these gene polymorphisms may help to better subgroup FMS patients and to guide a more rational pharmacological approach. Future genetic studies conducted in larger cohorts of FMS patients and matched control groups may further illuminate the role of genetics in FMS.

  9. Genetics Home Reference: Andersen-Tawil syndrome

    Science.gov (United States)

    ... The long QT syndrome family of cardiac ion channelopathies: a HuGE review. Genet Med. 2006 Mar;8( ... Tristani-Firouzi M, Etheridge SP. Kir 2.1 channelopathies: the Andersen-Tawil syndrome. Pflugers Arch. 2010 Jul; ...

  10. Genetics Home Reference: isolated Duane retraction syndrome

    Science.gov (United States)

    ... Encyclopedia: Extraocular Muscle Function Testing Health Topic: Eye Movement Disorders Genetic and Rare Diseases Information Center (1 link) Duane syndrome Additional NIH Resources (1 link) National Human Genome Research Institute: Learning About Duane Syndrome Educational Resources (9 links) American ...

  11. Genetics Home Reference: Chediak-Higashi syndrome

    Science.gov (United States)

    ... Higashi syndrome Health Topic: Immune System and Disorders Genetic and Rare Diseases Information Center (1 link) Chediak-Higashi syndrome Additional NIH Resources (1 link) National Institute of Allergy and Infectious Diseases: Primary Immune Deficiency Diseases Educational Resources (4 ...

  12. Genetic susceptibility and neurotransmitters in Tourette syndrome.

    Science.gov (United States)

    Paschou, Peristera; Fernandez, Thomas V; Sharp, Frank; Heiman, Gary A; Hoekstra, Pieter J

    2013-01-01

    Family studies have consistently shown that Tourette syndrome (TS) is a familial disorder and twin studies have clearly indicated a genetic contribution in the etiology of TS. Whereas early segregation studies of TS suggested a single-gene autosomal dominant disorder, later studies have pointed to more complex models including additive and multifactorial inheritance and likely interaction with genetic factors. While the exact cellular and molecular base of TS is as yet elusive, neuroanatomical and neurophysiological studies have pointed to the involvement of cortico-striato-thalamocortical circuits and abnormalities in dopamine, glutamate, gamma-aminobutyric acid, and serotonin neurotransmitter systems, with the most consistent evidence being available for involvement of dopamine-related abnormalities, that is, a reduction in tonic extracellular dopamine levels along with hyperresponsive spike-dependent dopamine release, following stimulation. Genetic and gene expression findings are very much supportive of involvement of these neurotransmitter systems. Moreover, intriguingly, genetic work on a two-generation pedigree has opened new research pointing to a role for histamine, a so far rather neglected neurotransmitter, with the potential of the development of new treatment options. Future studies should be aimed at directly linking neurotransmitter-related genetic and gene expression findings to imaging studies (imaging genetics), which enables a better understanding of the pathways and mechanisms through which the dynamic interplay of genes, brain, and environment shapes the TS phenotype. © 2013 Elsevier Inc. All rights reserved.

  13. Genetics Home Reference: antiphospholipid syndrome

    Science.gov (United States)

    ... Share: Email Facebook Twitter Home Health Conditions Antiphospholipid syndrome Antiphospholipid syndrome Printable PDF Open All Close All Enable ... area? Other Names for This Condition anti-phospholipid syndrome antiphospholipid antibody syndrome Hughes syndrome Related Information How are ...

  14. Genetics Home Reference: Jackson-Weiss syndrome

    Science.gov (United States)

    ... collapse boxes. Description Jackson-Weiss syndrome is a genetic disorder characterized by foot abnormalities and the premature fusion of certain skull bones (craniosynostosis). This early fusion ...

  15. Molecular-genetic risk assessement of determining angiotensin-converting enzyme hyperactivity in hemorrhagic fever with renal syndrome

    Directory of Open Access Journals (Sweden)

    Ildar R. Minniakhmetov

    2012-09-01

    Full Text Available The present study was designed to investigate changes in angiotensin-converting enzyme (ACE blood activity and angiotensin II type 1 receptor gene polymorphism as a possible disease predictor in hemorrhagic fever with renal syndrome (HFRS. Four hundred and nine patients (346 males and 63 females with HFRS serologic confirmation were enrolled in the study. Their age ranged from 15 to 65 years. ACE blood activity was assessed kinetically using the Bühlmann (Switzerland kit. Peripheral blood genomic DNA was isolated by a phenol-chloroform extraction. The genotyping of DNA loci was done using a polymerase chain reaction of DNA synthesis. Statistically, ACE blood activity was significantly higher throughout the entire HFRS course with diverse severity apart from the feverish phase of moderate-to-severe uncomplicated disease forms. *A1166 and *C1166 alleles, *A1166/*A1166 and *C1166/*C1166 genotypes of angiotensin II type 1 receptor gene were not associated with HFRS severity. The results of this study indicate that high ACE activity has not adaptive characteristics due to abnormalities in angiotensin II reception. It is an adequate metabolic response of the body to endotheliotropic virus activity.

  16. Clinical and molecular genetic analysis of a new mutation in children with Wolfram syndrome: a case report.

    Science.gov (United States)

    Xu, Qianqian; Qu, Huaiyu; Wei, Shihui

    2013-03-01

    A 12‑year‑old Chinese girl presented with gradual vision loss and insulin‑dependent diabetes mellitus and was suspected to suffer from Wolfram syndrome (WFS). A series of clinical examinations were performed, as well as direct DNA sequencing to screen the entire coding region of the WFS1 gene in the patient's family, including her parents and a brother. Ophthalmological examination revealed counting fingers/10 cm in the right eye and hand motions/10 cm in the left eye. Ophthalmoscopical examination identified bilateral optic atrophy without any signs of diabetic retinopathy. A hearing test was performed and revealed that the hearing ability for high frequency sounds was decreased. Urinary output in 24 h was >5,000 ml. In addition, a base substitution at c.2411T>C (Leu804Pro) in exon 8 was identified which was homozygous with the patient and heterozygous with the healthy parents and the brother. In the present case, a neuroophthalmology consult performed in the early stages of the disease was crucial for early diagnosis. In addition, this case study highlights the importance of performing a hearing test as well as collecting and analyzing 24‑h urine output in patients presenting with juvenile diabetes mellitus patients and optic atrophy without any signs of diabetic retinopathy.

  17. Genetics Home Reference: Schinzel-Giedion syndrome

    Science.gov (United States)

    ... Patel MS. Schinzel-Giedion syndrome: report of splenopancreatic fusion and proposed diagnostic criteria. Am J Med Genet ... 2010.01552.x. Citation on PubMed More from Genetics Home Reference Bulletins March is Trisomy Awareness Month ...

  18. Molecular genetics of hepatocellular neoplasia

    OpenAIRE

    Jain, Shilpa; Singhal, Shashideep; Lee, Peng; Xu, Ruliang

    2010-01-01

    Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the third leading cause of cancer deaths worldwide. Proper classification and early identification of HCC and precursor lesions is essential to the successful treatment and survival of HCC patients. Recent molecular genetic, pathologic, and clinical data have led to the stratification of hepatic adenomas into three subgroups: those with mutant TCF1/HNF1 α gene, those with mutant β-catenin, and those without mutations in ei...

  19. Cognitive and behavioral heterogeneity in genetic syndromes

    Directory of Open Access Journals (Sweden)

    Luiz F.L. Pegoraro

    2014-04-01

    Full Text Available OBJECTIVE: this study aimed to investigate the cognitive and behavioral profiles, as well as the psychiatric symptoms and disorders in children with three different genetic syndromes with similar sociocultural and socioeconomic backgrounds. METHODS: thirty-four children aged 6 to 16 years, with Williams-Beuren syndrome (n = 10, Prader-Willi syndrome (n = 11, and Fragile X syndrome (n = 13 from the outpatient clinics of Child Psychiatry and Medical Genetics Department were cognitively assessed through the Wechsler Intelligence Scale for Children (WISC-III. Afterwards, a full-scale intelligence quotient (IQ, verbal IQ, performance IQ, standard subtest scores, as well as frequency of psychiatric symptoms and disorders were compared among the three syndromes. RESULTS: significant differences were found among the syndromes concerning verbal IQ and verbal and performance subtests. Post-hoc analysis demonstrated that vocabulary and comprehension subtest scores were significantly higher in Williams-Beuren syndrome in comparison with Prader-Willi and Fragile X syndromes, and block design and object assembly scores were significantly higher in Prader-Willi syndrome compared with Williams-Beuren and Fragile X syndromes. Additionally, there were significant differences between the syndromes concerning behavioral features and psychiatric symptoms. The Prader-Willi syndrome group presented a higher frequency of hyperphagia and self-injurious behaviors. The Fragile X syndrome group showed a higher frequency of social interaction deficits; such difference nearly reached statistical significance. CONCLUSION: the three genetic syndromes exhibited distinctive cognitive, behavioral, and psychiatric patterns.

  20. Molecular and Genetic Aspects of Congenital Isolated Hypogonadotropic Hypogonadism.

    Science.gov (United States)

    Lima Amato, Lorena Guimaraes; Latronico, Ana Claudia; Gontijo Silveira, Leticia Ferreira

    2017-06-01

    Congenital isolated hypogonadotropic hypogonadism (IHH) is a clinically and genetically heterogenous disorder characterized by abnormal synthesis, secretion, or action of gonadotropin-releasing hormone, a key hypothalamic decapeptide that orchestrates the reproductive axis. Several modes of inheritance have been identified. A growing list of causative genes has been implicated in the molecular pathogenesis of syndromic and nonsyndromic IHH, largely contributing for better understanding the complex neuroendocrine control of reproduction. This article summarizes the great advances of molecular genetics of IHH and pointed up the heterogeneity and complexity of the genetic basis of this condition. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Hamartomatous polyps - a clinical and molecular genetic study

    DEFF Research Database (Denmark)

    Jelsig, Anne Marie

    2016-01-01

    the knowledge on clinical course and molecular genetics in patients with HPs and HPS, and to investigate research participants' attitude towards the results of extensive genetic testing. Paper I: In the first paper we investigated the occurrence, anatomic distribution, and other demographics of juvenile polyps......-Jeghers syndrome, and the PTEN hamartoma tumour syndrome. Currently, the HPS diagnoses are based on clinical criteria and are often assisted with genetic testing as candidate genes have been described for each syndrome. This thesis is based on six scientific papers. The overall aim of the studies was to expand......% fulfilled to diagnostic criteria of JPS. The majority of patients had a single juvenile polyp. Paper II: In this paper we conducted a review of the HPS based on the current literature. Paper III: We investigated the hypothesis that patients with one or few HPs may have a HPS based on genetic screening. We...

  2. Alport syndrome. Molecular genetic aspects

    DEFF Research Database (Denmark)

    Hertz, Jens Michael

    2009-01-01

    with a proximal breakpoint in COL4A5 intron 8 at Xq22.3, and a distal breakpoint in the RAB33A gene at Xq26.1. This rearrangement was exclusively ascertained by the Southern blotting analysis. Three deletions of >or= 2 exons were detected by MLPA. One of these was detected in a female proband. A deletion...... in heterozygous form will not be detected by PCR-SSCP or direct sequencing. A method based on the PCR-SSCP technique was set up for screening of the COL4A5 gene exon-by-exon for mutation. All 51 COL4A5 exons with flanking intronic sequences were screened by this technique. The two alternatively transcribed exons...... mutations, frame-shifts, and larger structural rearrangements, were found to cause a juvenile form of the disease with a mean age at ESRD of 21.6 years, compared to 33.1 years in patients with a non-truncating mutation. The effect of non-truncating mutations is, however, less clear-cut. Glycine...

  3. Genetics Home Reference: Poland syndrome

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions Poland syndrome Poland syndrome Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Poland syndrome is a disorder in which affected individuals ...

  4. Genetics Home Reference: Marfan syndrome

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions Marfan syndrome Marfan syndrome Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Marfan syndrome is a disorder that affects the connective tissue ...

  5. Genetics Home Reference: Wolfram syndrome

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions Wolfram syndrome Wolfram syndrome Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Wolfram syndrome is a condition that affects many of the ...

  6. Molecular genetic studies on obligate anaerobic bacteria

    International Nuclear Information System (INIS)

    Woods, D.R.

    1982-01-01

    Molecular genetic studies on obligate anaerobic bacteria have lagged behind similar studies in aerobes. However, the current interest in biotechnology, the involvement of anaerobes in disease and the emergence of antibioticresistant strains have focused attention on the genetics of anaerobes. This article reviews molecular genetic studies in Bacteroides spp., Clostridium spp. and methanogens. Certain genetic systems in some anaerobes differ from those in aerobes and illustrate the genetic diversity among bacteria

  7. Molecular genetics of hepatocellular neoplasia.

    Science.gov (United States)

    Jain, Shilpa; Singhal, Shashideep; Lee, Peng; Xu, Ruliang

    2010-01-23

    Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the third leading cause of cancer deaths worldwide. Proper classification and early identification of HCC and precursor lesions is essential to the successful treatment and survival of HCC patients. Recent molecular genetic, pathologic, and clinical data have led to the stratification of hepatic adenomas into three subgroups: those with mutant TCF1/HNF1 alpha gene, those with mutant beta-catenin, and those without mutations in either of these loci. Hepatic adenomas with alpha-catenin mutations have a significantly greater risk for malignant transformation in comparison with the other two subgroups. Telangiectatic focal nodular hyperplasia has now been reclassified as telangiectatic adenoma due to the presence of non-random methylation patterns, consistent with the monoclonal origin which is similar to hepatic adenoma and HCC. HCC precursor lesions demonstrate unique molecular alterations of HSP70, CAP2, glypican 3, and glutamine synthetase that have proven useful in the histologic diagnosis of early HCC. Though specific genetic alterations depend on HCC etiology, the main proteins affected include cell membrane receptors (in particular tyrosine kinase receptors) as well as proteins involved in cell signaling (specifically Wnt/beta-catenin, Ras/Raf/MEK/ERK and PI3K/Akt/mTOR pathways), cell cycle regulation (i.e. p53, p16/INK4, cyclin/cdk complex), invasiveness (EMT, TGF-beta) and DNA metabolism. Advances in gene expression profiling have provided new insights into the molecular genetics of HCC. HCCs can now be stratified into two clinically relevant groups: Class A, the low survival subclass (overall survival time 30.3+/- 8.02 months), shows strong expression signatures of cell proliferation and antiapoptosis genes (such as PNCA and cell cycle regulators CDK4, CCNB1, CCNA2, and CKS2) as well as genes involving ubiquitination and sumoylation; Class B, the high survival subclass (overall survival

  8. [Wolfram syndrome: clinical and genetic analysis in two sisters].

    Science.gov (United States)

    Conart, J-B; Maalouf, T; Jonveaux, P; Guerci, B; Angioi, K

    2011-10-01

    Wolfram syndrome is a severe genetic disorder defined by the association of diabetes mellitus, optic atrophy, deafness, and diabetes insipidus. Two sisters complained of progressive visual loss. Fundus examination evidenced optic atrophy. Their past medical history revealed diabetes mellitus and deafness since childhood. The association of these symptoms made the diagnosis of Wolfram syndrome possible. It was confirmed by molecular analysis, which evidenced composite WFS1 heterozygous mutations inherited from both their mother and father. Ophthalmologists should be aware of the possibility of Wolfram syndrome when diagnosing optic atrophy in diabetic children. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  9. Genetics Home Reference: Beckwith-Wiedemann syndrome

    Science.gov (United States)

    ... WN, Curley R, Macdonald F, Maher ER. Mitotic recombination and uniparental disomy in Beckwith-Wiedemann syndrome. Genomics. ... 43R-47R. Review. Citation on PubMed More from Genetics Home Reference Bulletins Rare Disease Day 2018 Darwin ...

  10. Genetics Home Reference: Ehlers-Danlos syndrome

    Science.gov (United States)

    ... c.31538. Epub 2017 Feb 1. Formal Treatment/Management Guidelines (7 links) Bowen JM, Sobey GJ, Burrows NP, Colombi M, Lavallee ME, Malfait F, Francomano CA. Ehlers-Danlos syndrome, classical type. Am J Med Genet C Semin Med ...

  11. Genetics Home Reference: Holt-Oram syndrome

    Science.gov (United States)

    ... navigation Home Page Search Home Health Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Share: Email ... from the University of Kansas Medical Center: Limb Anomalies GeneReviews (1 link) Holt-Oram Syndrome Scientific Articles ...

  12. Genetics Home Reference: auriculo-condylar syndrome

    Science.gov (United States)

    ... Health Topic: Jaw Injuries and Disorders Health Topic: Temporomandibular Joint Dysfunction Genetic and Rare Diseases Information Center (1 link) Auriculo-condylar syndrome Educational Resources (6 links) American ... InfoSearch: Dysgnathia Complex MalaCards: auriculo-condylar ...

  13. Genetics Home Reference: nail-patella syndrome

    Science.gov (United States)

    ... people with this condition, the areas at the base of the nails (lunulae) are triangular instead of ... Information from MedlinePlus (5 links) Diagnostic Tests Drug Therapy Genetic ... Manual Professional Version Orphanet: Nail-patella syndrome Resource list ...

  14. Genetics Home Reference: DICER1 syndrome

    Science.gov (United States)

    ... Encyclopedia: Sertoli-Leydig Cell Tumor Health Topic: Cancer Genetic and Rare Diseases Information Center (1 link) DICER1-related pleuropulmonary blastoma cancer predisposition syndrome Additional NIH Resources (1 link) National Cancer ...

  15. Genetic aspects of restless legs syndrome

    OpenAIRE

    Dhawan, V; Ali, M; Chaudhuri, K R

    2006-01-01

    Restless legs syndrome (RLS), also known as Ekbom syndrome, is a common movement disorder with sensorimotor symptoms occurring during sleep and quiet wakefulness. The underlying cause for RLS is unknown but genetic influences play a strong part in the pathogenesis of RLS, particularly when the condition starts at a young age. This review explores the genetic basis of RLS and related phenotypic variations. Recently, three loci showing vulnerability to RLS have been described in French‐Canadian...

  16. Genetics of migraine and related syndromes

    NARCIS (Netherlands)

    Stam, Anine Henrike

    2014-01-01

    In this dissertation clinical genetic investigations on migraine, related syndromes and comorbid conditions are described. The first migraine syndrome studied is Familial Hemiplegic Migraine (FHM), a monogenic migraine variant. The clinical spectrum of FHM1-3 and the relation with closely related

  17. Clinical and Molecular Genetic Analysis in Three Children with Wolfram Syndrome: A Novel WFS1 Mutation (c.2534T>A).

    Science.gov (United States)

    Çelmeli, Gamze; Türkkahraman, Doğa; Çürek, Yusuf; Houghton, Jayne; Akçurin, Sema; Bircan, İffet

    2017-03-01

    Wolfram syndrome (WS) is an autosomal recessive disorder caused by mutations in WFS1 gene. The clinical features include diabetes insipidus, diabetes mellitus (DM), optic atrophy, deafness, and other variable clinical manifestations. In this paper, we present the clinical and genetic characteristics of 3 WS patients from 3 unrelated Turkish families. Clinical characteristics of the patients and the age of onset of symptoms were quite different in each pedigree. The first two cases developed all symptoms of the disease in their first decade of life. The heterozygous father of case 2 was symptomatic with bilateral deafness. The first ocular finding of one patient (patient 3) was bilateral cataract which was accompanying DM as a first feature of the syndrome. In this patient's family, there were two members with features suggestive of WS. Previously known homozygous mutations, c.460+1G>A in intron 4 and c.1885C>T in exon 8, were identified in these cases. A novel homozygous c.2534T>A mutation was also detected in the exon 8 of WFS1 gene. Because of the rarity and heterogeneity of WS, detection of specific and nonspecific clinical signs including ocular findings and family history in non-autoimmune, insulinopenic diabetes cases should lead to a tentative diagnosis of WS. Genetic testing is required to confirm the diagnosis.

  18. Genetics Home Reference: Bloom syndrome

    Science.gov (United States)

    ... 1 link) Bloom syndrome Sources for This Page Amor-Guéret M. Bloom syndrome, genomic instability and cancer: ... Zhang B, Zhang XD, Dou SX, Wang PY, Amor-Gueret M, Xi XG. Structural and functional analyses ...

  19. Genetics Home Reference: CHARGE syndrome

    Science.gov (United States)

    ... combination of major and minor characteristics. The major characteristics of CHARGE syndrome are common in this disorder and occur less ... and unusually shaped external ears. While the minor characteristics of CHARGE syndrome are common in this disorder, they are also ...

  20. Genetics Home Reference: Pendred syndrome

    Science.gov (United States)

    ... aqueduct (EVA) is a characteristic feature of Pendred syndrome . The vestibular aqueduct is a bony canal that connects the ... of Philadelphia, Center for Childhood Communication GeneReview: Pendred Syndrome/Nonsyndromic Enlarged Vestibular ... Encyclopedia: Hearing Loss ...

  1. Molecular genetics of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Radice, P.; Pierotti, M. A. [Istituto Nazionale dei Tumori, Milan (Italy). Division of Experimental Oncology

    1997-09-01

    In the last two decades, molecular studies have enlightened the complexity of the genetic alterations that occur in breast cancer cells. To date, more than 40 different genes or loci have been found to be altered in breast carcinomas. Although some of these genes, as for example ERBB2, appear to be mutated in a high proportion of cases, their mechanism of action and their role in the different stages of cancer development are still poorly understood. More recently, two major determinants of the inherited predisposition to breast cancer, BRCA1 and BRCA2, have been isolated. As a consequence, it is now possible to screen families with a positive history of breast carcinomas for the identification of mutations carriers, in order to address these individuals into adequate programs of cancer surveillance and prevention.

  2. Molecular genetics of breast cancer

    International Nuclear Information System (INIS)

    Radice, P.; Pierotti, M. A.

    1997-01-01

    In the last two decades, molecular studies have enlightened the complexity of the genetic alterations that occur in breast cancer cells. To date, more than 40 different genes or loci have been found to be altered in breast carcinomas. Although some of these genes, as for example ERBB2, appear to be mutated in a high proportion of cases, their mechanism of action and their role in the different stages of cancer development are still poorly understood. More recently, two major determinants of the inherited predisposition to breast cancer, BRCA1 and BRCA2, have been isolated. As a consequence, it is now possible to screen families with a positive history of breast carcinomas for the identification of mutations carriers, in order to address these individuals into adequate programs of cancer surveillance and prevention

  3. Advances in molecular genetic studies of primary dystonia

    Directory of Open Access Journals (Sweden)

    MA Ling-yan

    2013-07-01

    Full Text Available Dystonias are heterogeneous hyperkinetic movement disorders characterized by involuntary muscle contractions which result in twisting, repetitive movements and abnormal postures. In recent years, there was a great advance in molecular genetic studies of primary dystonia. This paper will review the clinical characteristics and molecular genetic studies of primary dystonia, including early-onset generalized torsion dystonia (DYT1, whispering dysphonia (DYT4, dopa-responsive dystonia (DYT5, mixed-type dystonia (DYT6, paroxysmal kinesigenic dyskinesia (DYT10, myoclonus-dystonia syndrome (DYT11, rapid-onset dystonia parkinsonism (DYT12, adult-onset cervical dystonia (DYT23, craniocervical dystonia (DYT24 and primary torsion dystonia (DYT25.

  4. Periodontal disease in individuals with Down Syndrome: genetic focus

    Directory of Open Access Journals (Sweden)

    Lícia Bezerra Cavalcante

    2009-12-01

    Full Text Available Fundamental concepts of etiology, inheritance and clinical characteristics of Down syndrome are used in this review as a basis for submission of studies that focus on periodontal disease in individuals with Down syndrome, since almost 100% of them develop the disease in adult life. It is believed that in association with environmental and cultural factors related to hygiene and disabilities of coordination, the immunological characteristics that are found altered in individuals with Down syndrome, such as deficient neutrophil chemotaxis and reduced number of mature T lymphocytes, may contribute to the greater prevalence and severity of periodontal involvement in patients with Down syndrome. Moreover, the pattern of periodontal destruction observed in individuals with Down syndrome is consistent with aggressive periodontitis, with a predominance of periodontopathogens such as Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Tannerella forsythensis during childhood and adolescence of Down’s syndrome patients. It is possible to note a relationship between the development of molecular techniques and the evolution of knowledge about Down syndrome, for example: identification of the trisomy syndrome by observing only part of chromosome 21 (distal long arm; identification of genes in this trisomic region and the pattern of superexpression (or not of these genes. Moreover, in this review future perspectives are presented with regard to better understanding Down syndrome in the genetic context, which will reflect in more individualized and effective clinical treatments that will provide these patients with a better quality of life.

  5. Genetics Home Reference: KBG syndrome

    Science.gov (United States)

    ... syndrome Patient Support and Advocacy Resources (8 links) American Association on Intellectual and Developmental Disabilities Children's Craniofacial Association Human Growth Foundation KBG Foundation ...

  6. Genetics Home Reference: Kleefstra syndrome

    Science.gov (United States)

    ... PDF) Patient Support and Advocacy Resources (6 links) American Association on Intellectual and Developmental Disabilities Chromosome Disorder Outreach GeneSpark.org Kleefstra Syndrome Community ...

  7. (-)-Menthol biosynthesis and molecular genetics

    Science.gov (United States)

    Croteau, Rodney B.; Davis, Edward M.; Ringer, Kerry L.; Wildung, Mark R.

    2005-12-01

    (-)-Menthol is the most familiar of the monoterpenes as both a pure natural product and as the principal and characteristic constituent of the essential oil of peppermint ( Mentha x piperita). In this paper, we review the biosynthesis and molecular genetics of (-)-menthol production in peppermint. In Mentha species, essential oil biosynthesis and storage is restricted to the peltate glandular trichomes (oil glands) on the aerial surfaces of the plant. A mechanical method for the isolation of metabolically functional oil glands, has provided a system for precursor feeding studies to elucidate pathway steps, as well as a highly enriched source of the relevant biosynthetic enzymes and of their corresponding transcripts with which cDNA libraries have been constructed to permit cloning and characterization of key structural genes. The biosynthesis of (-)-menthol from primary metabolism requires eight enzymatic steps, and involves the formation and subsequent cyclization of the universal monoterpene precursor geranyl diphosphate to the parent olefin (-)-(4 S)-limonene as the first committed reaction of the sequence. Following hydroxylation at C3, a series of four redox transformations and an isomerization occur in a general “allylic oxidation-conjugate reduction” scheme that installs three chiral centers on the substituted cyclohexanoid ring to yield (-)-(1 R, 3 R, 4 S)-menthol. The properties of each enzyme and gene of menthol biosynthesis are described, as are their probable evolutionary origins in primary metabolism. The organization of menthol biosynthesis is complex in involving four subcellular compartments, and regulation of the pathway appears to reside largely at the level of gene expression. Genetic engineering to up-regulate a flux-limiting step and down-regulate a side route reaction has led to improvement in the composition and yield of peppermint oil.

  8. Genetics Home Reference: Lynch syndrome

    Science.gov (United States)

    ... features of neurofibromatosis in HNPCC families with homozygous mismatch repair gene mutations. Fam Cancer. 2005;4(4):323-33. ... of mismatch repair and the functional analysis of mismatch repair defects in Lynch syndrome. Fam Cancer. 2013 ... P. Lynch syndrome genes. Fam Cancer. 2005;4(3):227-32. Review. ...

  9. Genetics Home Reference: WAGR syndrome

    Science.gov (United States)

    ... retardation syndrome Sources for This Page Breslow NE, Norris R, Norkool PA, Kang T, Beckwith JB, Perlman EJ, Ritchey ML, Green DM, Nichols KE; National Wilms Tumor Study Group. Characteristics and outcomes of children with the Wilms tumor-Aniridia syndrome: a report ...

  10. Genetics Home Reference: PURA syndrome

    Science.gov (United States)

    ... tone (hypotonia) and feeding difficulties. Problems with swallowing (dysphagia) can last throughout life. In addition, affected infants ... Drug Therapy Genetic Counseling Palliative Care Surgery and Rehabilitation Related Information How are genetic conditions diagnosed? How ...

  11. Investigation of 305 patients with myelodysplastic syndromes and 20q deletion for associated cytogenetic and molecular genetic lesions and their prognostic impact.

    Science.gov (United States)

    Bacher, Ulrike; Haferlach, Torsten; Schnittger, Susanne; Zenger, Melanie; Meggendorfer, Manja; Jeromin, Sabine; Roller, Andreas; Grossmann, Vera; Krauth, Maria-Theresa; Alpermann, Tamara; Kern, Wolfgang; Haferlach, Claudia

    2014-03-01

    In patients with myelodysplastic syndromes (MDS), sole 20q deletion [del(20q)] is a recurrent favourable abnormality. We studied additional molecular and cytogenetic lesions and their prognostic impact in 305 MDS patients with del(20q) (229 males/76 females; 29-90 years). All patients were investigated by cytomorphology and chromosome banding analysis (CBA), subsets by fluorescence in situ hybridization, molecular mutation screening, and array comparative genomic hybridization (aCGH). By aCGH (n = 30), the minimal common deleted region (CDR) was flanked by PTPRT (20q13·11) and EYA2 (20q13·12). 210 (68·9%) patients had 'early MDS' without blast increase, 95 (31·1%) 'advanced' MDS with blast increase (5-19%). Additional chromosomal abnormalities (ACAs) were detected in 88/305 (28·9%) patients. Patients with advanced MDS more frequently had ACAs (P = 0·003) and had a higher mean number of ACAs (P = 0·020) and of molecular mutations (P = 0·060). Spliceosome mutations were frequent (U2AF1: n = 31/155; 20·0%; SRSF2: n = 31/159; 19·5%; SF3B1mut: n = 8/159; 5·0%). ASXL1mut (25/153; 16·3%) were associated with advanced MDS (P = 0·001). Presence of ≥3 ACAs (P = 0·003) and ASXL1mut (P = 0·002) were associated with worse 2-year survival. In conclusion, the cytogenetic subgroup of MDS with del(20q) has a good prognosis but may be further subclassified by additional cytogenetic and molecular lesions. U2AF1mut is overrepresented in MDS with del(20q), and ASXL1mut is prognostically adverse. © 2013 John Wiley & Sons Ltd.

  12. Genetics Home Reference: Netherton syndrome

    Science.gov (United States)

    ... experience outbreaks of a distinctive skin abnormality called ichthyosis linearis circumflexa, involving patches of multiple ring-like ... syndrome ichthyosiform erythroderma with hypotrichosis and hyper-IgE ichthyosis linearis circumflexa ILC NETH Netherton disease NS Related ...

  13. Genetics Home Reference: Turner syndrome

    Science.gov (United States)

    ... Sep 7. Citation on PubMed Hong D, Scaletta Kent J, Kesler S. Cognitive profile of Turner syndrome. Dev ... Institutes of Health National Library of Medicine Lister Hill National Center for Biomedical Communications 8600 Rockville Pike, ...

  14. Genetics Home Reference: Alagille syndrome

    Science.gov (United States)

    ... abnormalities. This combination of heart defects is called tetralogy of Fallot . People with Alagille syndrome may have distinctive facial ... the disorder, such as a heart defect like tetralogy of Fallot, or a characteristic facial appearance. These individuals do ...

  15. Genetics Home Reference: Gitelman syndrome

    Science.gov (United States)

    ... a potentially dangerous abnormal heart rhythm called ventricular arrhythmia. The signs and symptoms of Gitelman syndrome vary ... Celebrates Its 15th Anniversary National DNA Day 2018 Newborn Screening Saves Lives Act Turns 10 All Bulletins ...

  16. Genetics Home Reference: Cowden syndrome

    Science.gov (United States)

    ... often beginning in their thirties or forties. Other diseases of the breast, thyroid, and endometrium are also common in Cowden syndrome . Additional signs and symptoms can include an enlarged head ( macrocephaly ) and a ...

  17. Genetics Home Reference: Tourette syndrome

    Science.gov (United States)

    ... or noises called tics. Tics usually appear in childhood, and their severity varies over time. In most cases, tics become milder and less frequent in late adolescence and adulthood. Tourette syndrome involves both motor tics, ...

  18. Genetics Home Reference: Gillespie syndrome

    Science.gov (United States)

    ... and coordinating movements (ataxia), and mild to moderate intellectual disability. Gillespie syndrome is characterized by aniridia , which is ... Other Names for This Condition aniridia-cerebellar ataxia-intellectual disability aniridia-cerebellar ataxia-mental deficiency aniridia, cerebellar ataxia, ...

  19. Genetics Home Reference: Knobloch syndrome

    Science.gov (United States)

    ... the central area of the retina, called the macula. The macula is responsible for sharp central vision, which is ... Due to abnormalities in the vitreous, retina, and macula, people with Knobloch syndrome often develop blindness in ...

  20. Genetics Home Reference: Meckel syndrome

    Science.gov (United States)

    ... kidneys with numerous fluid-filled cysts ; an occipital encephalocele , which is a sac-like protrusion of the ... link) National Institute of Neurological Disorders and Stroke: Encephaloceles Educational Resources (3 links) MalaCards: meckel syndrome, type ...

  1. Genetics Home Reference: Emanuel syndrome

    Science.gov (United States)

    ... of Emanuel syndrome include an unusually small head ( microcephaly ), distinctive facial features, and a small lower jaw ( ... MedlinePlus Encyclopedia: Cleft Lip and Palate MedlinePlus Encyclopedia: Microcephaly MedlinePlus Encyclopedia: Preauricular Tag or Pit General Information ...

  2. Genetics Home Reference: Feingold syndrome

    Science.gov (United States)

    ... Feingold syndrome include an unusually small head size ( microcephaly ), a small jaw ( micrognathia ), a narrow opening of ... Duodenal Atresia MedlinePlus Encyclopedia: Esophageal Atresia MedlinePlus Encyclopedia: Microcephaly MedlinePlus Encyclopedia: Webbing of the Fingers or Toes ...

  3. Genetics Home Reference: Roberts syndrome

    Science.gov (United States)

    ... nose. They may have a small head size ( microcephaly ), and in severe cases affected individuals have a ... Roberts Syndrome MedlinePlus Encyclopedia: Contracture deformity MedlinePlus Encyclopedia: Microcephaly General Information from MedlinePlus (5 links) Diagnostic Tests ...

  4. Genetics Home Reference: Sotos syndrome

    Science.gov (United States)

    ... gene are the primary cause of Sotos syndrome , accounting for up to 90 percent of cases. Other ... Support and Advocacy Resources (6 links) Child Growth Foundation (UK) National Organization for Rare Disorders (NORD) Resource ...

  5. Genetics Home Reference: Proteus syndrome

    Science.gov (United States)

    ... now follow a set of strict guidelines that define the signs and symptoms of Proteus syndrome . Related ... for Links Data Files & API Site Map Subscribe Customer Support USA.gov Copyright Privacy Accessibility FOIA Viewers & ...

  6. Genetics Home Reference: Tietz syndrome

    Science.gov (United States)

    ... called melanocytes . Within these cells, this protein controls production of the pigment melanin, which contributes to hair, eye, and skin ... inner ear leads to hearing loss. Decreased melanin production (hypopigmentation) ... epithelium changes that are characteristic of Tietz syndrome . ...

  7. Genetics Home Reference: Lowe syndrome

    Science.gov (United States)

    ... in the legs. Progressive kidney problems in older children and adults with Lowe syndrome can lead to life-threatening renal failure and end-stage renal disease (ESRD). Related Information What does it mean if ...

  8. Genetics Home Reference: Aicardi syndrome

    Science.gov (United States)

    ... corpus callosum ). They have seizures beginning in infancy (infantile spasms), which tend to progress to recurrent seizures (epilepsy) ... with chorioretinal abnormality agenesis of corpus callosum with infantile spasms and ocular abnormalities Aicardi's syndrome callosal agenesis and ...

  9. Meckel Syndrome: Genetics, Perinatal Findings, and Differential Diagnosis

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2007-03-01

    Full Text Available Meckel syndrome (MKS is a lethal, autosomal recessive disorder characterized by occipital encephalocele, bilateral renal cystic dysplasia, hepatic ductal proliferation, fibrosis and cysts, and polydactyly. Genetic heterogeneity of MKS has been established by three reported MKS loci, i.e., MKS1 on 17q23, MKS2 on 11q13, and MKS3 on 8q21.13-q22.1. MKS1 encodes a component of flagellar apparatus basal body proteome, which is associated with ciliary function. MKS3 encodes a seven-transmembrane receptor protein, meckelin. The identification of the MKS3 gene as well as the MKS1 gene enables molecular genetic testing for at-risk families, and allows accurate genetic counseling, carrier testing, and prenatal diagnosis. Pregnancies with MKS fetuses may be associated with an elevated maternal serum α-fetoprotein level and an abnormal screening result in the second-trimester maternal serum screening test. The classic MKS triad of occipital encephalocele, postaxial polydactyly, and bilateral enlarged multicystic kidneys can be diagnosed before the 14th gestational weeks by ultrasonography. However, later in pregnancy, severe oligohydramnios may make the diagnosis of polydactyly and encephalocele difficult. Differential diagnosis for MKS includes autosomal recessive polycystic kidney disease, trisomy 13, Smith-Lemli-Opitz syndrome, hydrolethalus syndrome, Senior-Loken syndrome, Joubert syndrome, Bardet-Biedl syndrome, and oral-facial-digital syndrome type 1. This article provides an overview of genetics, perinatal findings, and differential diagnosis of MKS. The ciliopathy underlies the pathogenesis of MKS. Prenatal diagnosis of bilateral enlarged multicystic kidneys should alert MKS and prompt a thorough investigation of central nervous system malformations and polydactyly.

  10. Genetic epidemiology of Down syndrome in Iran

    Directory of Open Access Journals (Sweden)

    Manoochehr Shariati

    2005-02-01

    Full Text Available Down syndrome is the most common autosomal abnormality and occurs in approximately 1 per 700 live births. Down syndrome accounts for about one third of all moderate and sever mental handicaps in school-aged children. To reveal genetic epidemiology of Down syndrome, 545 karyotypes of referred cases to the author were evaluated. The frequencies of three cytogenetic variants of Down syndrome were trisomy 21 (77.5%, mosaicism (18% and chromosomal translocation (4.5%. Male to female ratio was 1.34. The mean age of their mothers and fathers were 29.03 years (median=27 years and 34.6 years (median=33 years, respectively. Therefore, mean age of Iranian mothers with Down syndrome is six years less than those in the western countries.

  11. Genetic Counselling for Schizophrenia in the Era of Molecular Genetics

    Science.gov (United States)

    Hodgkinson, Kathleen A; Murphy, Jillian; O’Neill, Sheri; Brzustowicz, Linda; Bassett, Anne S

    2012-01-01

    Objective To review the role of genetic counselling for individuals with psychiatric illnesses. Method Using schizophrenia as an example and including updated information about a genetic subtype (22q deletion syndrome), we discuss the value of the genetic counselling process in psychiatry, with support from the literature and our clinical experience. Results Genetic counselling, the process through which knowledge about the genetics of illnesses is shared, provides information on the inheritance of illnesses and their recurrence risks; addresses the concerns of patients, their families, and their health care providers; and supports patients and their families dealing with these illnesses. For comprehensive medical management, this service should be available to all individuals with schizophrenia and their families. Conclusions New findings in the genetics of psychiatric illness may have important clinical implications for patients and their families. PMID:11280080

  12. Genetics and molecular biology of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    King, M.C. [California Univ., Berkeley, CA (United States); Lippman, M. [Georgetown Univ. Medical Center, Washington, DC (United States)] [comps.

    1992-12-31

    This volume contains the abstracts of oral presentations and poster sessions presented at the Cold Springs Harbor Meeting on Cancer Cells, this meeting entitled Genetics and Molecular Biology of Breast Cancer.

  13. Genetics Home Reference: Arts syndrome

    Science.gov (United States)

    ... atrophy Patient Support and Advocacy Resources (5 links) American Foundation for the Blind Hearing Health Foundation National Association of the Deaf National Ataxia Foundation The Arc: For People with Intellectual and Developmental Disabilities GeneReviews (1 link) Arts Syndrome ClinicalTrials.gov (1 ...

  14. Genetics Home Reference: Werner syndrome

    Science.gov (United States)

    ... United States. This syndrome occurs more often in Japan, affecting 1 in 20,000 to 1 in ... Reviewed : December 2012 Published : March 6, 2018 The resources on this site should not be used as a substitute for ... of Health & Human Services National Institutes of Health National Library of ...

  15. Genetics Home Reference: Laron syndrome

    Science.gov (United States)

    ... feet. Adults with this condition tend to develop obesity. However, the signs and symptoms of Laron syndrome vary, even among affected members of the same family. Studies suggest that people with Laron ... relatives, despite having obesity (a risk factor for both cancer and type ...

  16. Genetics Home Reference: MEGDEL syndrome

    Science.gov (United States)

    ... improve by early childhood; and episodes of abnormally high amounts of lactic acid in the blood (lactic acidosis). The life expectancy of individuals ... deafness, encephalopathy, and Leigh-like syndrome (MEGDEL association) in four ... feature: proper classification and nomenclature. J Inherit Metab Dis. 2013 Nov; ...

  17. Genetics Home Reference: Yao syndrome

    Science.gov (United States)

    ... than half of affected individuals. Dry eyes and dry mouth (described as "sicca-like" symptoms, which refers to dryness) are reported in about half of people with this disease. Other potential signs and symptoms of Yao syndrome include mouth sores, chest pain, and enlargement of ...

  18. Genetics Home Reference: Kabuki syndrome

    Science.gov (United States)

    ... also have seizures, an unusually small head size ( microcephaly ), or weak muscle tone (hypotonia). Some have eye ... Syndrome ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific Articles on PubMed (1 link) PubMed OMIM (2 links) ...

  19. Genetics Home Reference: Angelman syndrome

    Science.gov (United States)

    ... recurrent seizures (epilepsy) and a small head size ( microcephaly ). Delayed development becomes noticeable by the age of ... Syndrome ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific Articles on PubMed (1 link) PubMed OMIM (1 link) ...

  20. Protocols in human molecular genetics

    National Research Council Canada - National Science Library

    Mathew, Christopher G

    1991-01-01

    ... sequences has led to the development of DNA fingerprinting. The application of these techniques to the study of the human genome has culminated in major advances such as the cloning of the cystic fibrosis gene, the construction of genetic linkage maps of each human chromosome, the mapping of many genes responsible for human inherited disorders, genet...

  1. Genetics Home Reference: CHOPS syndrome

    Science.gov (United States)

    ... Defects Patient Support and Advocacy Resources (4 links) American Heart Association Contact a Family: Heart Defects The Arc: For People with Intellectual and Developmental Disabilities University of Kansas Genetics Education Center Resource List: ...

  2. Genetics Home Reference: Stormorken syndrome

    Science.gov (United States)

    ... lack of a functioning spleen (asplenia), scaly skin (ichthyosis), headaches, and difficulty with reading and spelling (dyslexia). ... thrombocytopathia, muscle fatigue, asplenia, miosis, migraine, dyslexia and ichthyosis. Clin Genet. 1985 Nov;28(5):367-74. ...

  3. Genetics Home Reference: Clouston syndrome

    Science.gov (United States)

    ... junctions, which permit the transport of nutrients, charged atoms (ions), and signaling molecules between neighboring cells. The ... direct-to-consumer genetic testing? What is precision medicine? What is newborn screening? New Pages Obstructive sleep ...

  4. Genetics Home Reference: Christianson syndrome

    Science.gov (United States)

    ... acts as a channel to exchange positively charged atoms (ions) of sodium (Na+) with hydrogen ions (H+). ... direct-to-consumer genetic testing? What is precision medicine? What is newborn screening? New Pages Obstructive sleep ...

  5. Genetics Home Reference: Brugada syndrome

    Science.gov (United States)

    ... sodium channel, which normally transports positively charged sodium atoms (ions) into heart muscle cells. This type of ... direct-to-consumer genetic testing? What is precision medicine? What is newborn screening? New Pages Obstructive sleep ...

  6. Genetics Home Reference: Andermann syndrome

    Science.gov (United States)

    ... cotransporter. This protein is involved in moving charged atoms (ions) of potassium (K) and chlorine (Cl) across ... direct-to-consumer genetic testing? What is precision medicine? What is newborn screening? New Pages Obstructive sleep ...

  7. Genetics Home Reference: Bartter syndrome

    Science.gov (United States)

    ... transport also affect the reabsorption of other charged atoms (ions), including potassium and calcium. The resulting imbalance ... direct-to-consumer genetic testing? What is precision medicine? What is newborn screening? New Pages Obstructive sleep ...

  8. Genetics Home Reference: Joubert syndrome

    Science.gov (United States)

    ... such as Ashkenazi Jewish, French-Canadian, and Hutterite populations. Related Information What information about a genetic condition ... of many types of cells, including brain cells (neurons) and certain cells in the kidneys and liver. ...

  9. Genetics Home Reference: Cockayne syndrome

    Science.gov (United States)

    ... disorder characterized by an abnormally small head size (microcephaly), a failure to gain weight and grow at ... Drug: Metronidazole Oral Encyclopedia: Failure to Thrive Encyclopedia: Microcephaly Health Topic: Growth Disorders Genetic and Rare Diseases ...

  10. Genetics Home Reference: Fraser syndrome

    Science.gov (United States)

    ... navigation Home Page Search Home Health Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Share: Email ... of the genitalia and the urinary tract (genitourinary anomalies). Other tissues and organs can also be affected. ...

  11. Genetics Home Reference: Grange syndrome

    Science.gov (United States)

    ... X, Yang ML; University of Washington Center for Mendelian Genomics, Bamshad MJ, Nickerson DA, Gornik HL, Ganesh ... 3):190-5. Citation on PubMed More from Genetics Home Reference Bulletins March is Trisomy Awareness Month ...

  12. Genetics Home Reference: 3-M syndrome

    Science.gov (United States)

    ... ubiquitin-proteasome system acts as the cell's quality control system by disposing of damaged, misshapen, and excess proteins. This ... of short stature syndrome with novel CUL7 mutation in Yakuts: new population isolate in Asia. J Med Genet. 2007 Dec;44(12):772- ...

  13. Genetic Susceptibility and Neurotransmitters in Tourette Syndrome

    NARCIS (Netherlands)

    Paschou, Peristera; Fernandez, Thomas V.; Sharp, Frank; Heiman, Gary A.; Hoekstra, Pieter J.; Martino, D; Cavanna, AE

    2013-01-01

    Family studies have consistently shown that Tourette syndrome (TS) is a familial disorder and twin studies have clearly indicated a genetic contribution in the etiology of TS. Whereas early segregation studies of TS suggested a single-gene autosomal dominant disorder, later studies have pointed to

  14. The genetic basis of colonic adenomatous polyposis syndromes.

    Science.gov (United States)

    Talseth-Palmer, Bente A

    2017-01-01

    Colorectal cancer (CRC) is one of the most common forms of cancer worldwide and familial adenomatous polyposis (FAP) accounts for approximately 1% of all CRCs. Adenomatous polyposis syndromes can be divided into; familial adenomatous polyposis (FAP) - classic FAP and attenuated familial adenomatous polyposis (AFAP), MUTYH-associated polyposis (MAP), NTHL1-associated polyposis (NAP) and polymerase proofreading-associated polyposis (PPAP). The polyposis syndromes genetics and clinical manifestation of disease varies and cases with clinical diagnosis of FAP might molecularly show a different diagnosis. This review examines different aspects of the adenomatous polyposis syndromes genetics and clinical manifestation of disease; in addition the genotype-phenotype and modifier alleles of FAP will be discussed. New technology has made it possible to diagnose some of the APC mutation negative patients into their respective syndromes. There still remain many molecularly undiagnosed adenomatous polyposis patients indicating that there remain causative genes to be discovered and with today's technology these are expected to be identified in the near future. The knowledge about the role of modifier alleles in FAP will contribute to improved pre-symptomatic diagnosis and treatment. New novel mutations will continually be discovered in genes already associated with disease and new genes will be discovered that are associated with adenomatous polyposis. The search for modifier alleles in FAP should be made a priority.

  15. Molecular diversity and genetic relationships in Secale

    Indian Academy of Sciences (India)

    Molecular diversity and genetic relationships in Secale. E. Santos, M. Matos, P. Silva, A. M. Figueiras, C. Benito and O. Pinto-Carnide. J. Genet. 95, 273–281. Table 1. RAPD and ISSR primers used in this study. Primer. 5 –3. Primer. 5 –3. RAPDs (Operon). A1. CAGGCCCTTC. C5. CATGACCGCC. A4. AATCGGGCTG. C6.

  16. Molecular diversity and genetic relationships in Secale

    Indian Academy of Sciences (India)

    Supplementary data: Molecular diversity and genetic relationships in Secale. E. Santos, M. Matos, P. Silva, A. M. Figueiras, C. Benito and O. Pinto-Carnide. J. Genet. 95, 273–281. Table 1. RAPD and ISSR primers used in this study. Primer. 5 –3. Primer. 5 –3. RAPDs (Operon). A1. CAGGCCCTTC. C5. CATGACCGCC. A4.

  17. Molecular markers unravel intraspecific and interspecific genetic ...

    Indian Academy of Sciences (India)

    Molecular markers unravel intraspecific and interspecific genetic variability in Plantago ovata and some of its wild allies. Shivanjali Kotwal, Manoj K. Dhar, Balbir Kour, Kuldeep Raj and Sanjana Kaul. J. Genet. 92, 293–298. Table 1. Jaccard's similarity matrix of AFLP analysis of Plantago species. P. coronopus P. lanceolata ...

  18. Genetics of human Bardet-Biedl syndrome, an updates.

    Science.gov (United States)

    Khan, S A; Muhammad, N; Khan, M A; Kamal, A; Rehman, Z U; Khan, S

    2016-07-01

    Bardet-Biedl syndrome (BBS) is an autosomal recessive multisystemic human genetic disorder characterized by six major defects including obesity, mental retardation, renal anomalies, polydactyly, retinal degeneration and hypogenitalism. In several cases of BBS, few other features such as metabolic defects, cardiovascular anomalies, speech deficits, hearing loss, hypertension, hepatic defects and high incidence of diabetes mellitus have been reported as well. The BBS displays extensive genetic heterogeneity. To date, 19 genes have been mapped on different chromosomes causing BBS phenotypes having varied mutational load of each BBS gene. In this review, we have discussed clinical spectrum and genetics of BBS. This report presents a concise overview of the current knowledge on clinical data and its molecular genetics progress upto date. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Molecular changes in fetal Down syndrome brain.

    Science.gov (United States)

    Engidawork, Ephrem; Lubec, Gert

    2003-03-01

    Trisomy of human chromosome 21 is a major cause of mental retardation and other phenotypic abnormalities collectively known as Down syndrome. Down syndrome is associated with developmental failure followed by processes of neurodegeneration that are known to supervene later in life. Despite a widespread interest in Down syndrome, the cause of developmental failure is unclear. The brain of a child with Down syndrome develops differently from that of a normal one, although characteristic morphological differences have not been noted in prenatal life. On the other hand, a review of the existing literature indicates that there are a series of biochemical alterations occurring in fetal Down syndrome brain that could serve as substrate for morphological changes. We propose that these biochemical alterations represent and/or precede morphological changes. This review attempts to dissect these molecular changes and to explain how they may lead to mental retardation.

  20. Molecular genetics of intellectual disability

    OpenAIRE

    Bessa, C.; Lopes, Fátima; Maciel, P.

    2012-01-01

    The goal of this chapter is to review the current knowledge of the genetic causes of intellectual disability, focusing on alterations at the chromosomal and single gene level, with particular mention to the new technological developments, including array technologies and next-generation sequencing, which allowed an enormous increase in yield from genetic studies. The cellular and physiological pathways that seem to be most affected in intellectual disability will also be addressed. Fina...

  1. Genetics Home Reference: Down syndrome

    Science.gov (United States)

    ... in cell division called nondisjunction results in a reproductive cell with an abnormal number of chromosomes. For example, an egg or sperm cell may gain an extra copy of chromosome 21 . If one of these atypical reproductive cells contributes to the genetic makeup of a ...

  2. Genetics Home Reference: Klinefelter syndrome

    Science.gov (United States)

    ... in cell division called nondisjunction results in a reproductive cell with an abnormal number of chromosomes. For example, an egg or sperm cell may gain one or more extra copies of the X chromosome as a result ... of these atypical reproductive cells contributes to the genetic makeup of a ...

  3. Genetics Home Reference: Maffucci syndrome

    Science.gov (United States)

    ... Boon LM, Vikkula M, Kurek KC, Szuhai K, French PJ, Bovée JV. Somatic mosaic IDH1 and IDH2 ... or Free article on PubMed Central More from Genetics Home Reference Bulletins March is Trisomy Awareness Month ...

  4. Clinical applications of schizophrenia genetics: genetic diagnosis, risk, and counseling in the molecular era

    Directory of Open Access Journals (Sweden)

    Costain G

    2012-02-01

    Full Text Available Gregory Costain1,2, Anne S Bassett1–41Clinical Genetics Research Program, Centre for Addiction and Mental Health, 2Institute of Medical Science, University of Toronto, 3Division of Cardiology, Department of Medicine and Department of Psychiatry, University Health Network, 4Department of Psychiatry, University of Toronto, Toronto, Ontario, CanadaAbstract: Schizophrenia is a complex neuropsychiatric disease with documented clinical and genetic heterogeneity, and evidence for neurodevelopmental origins. Driven by new genetic technologies and advances in molecular medicine, there has recently been concrete progress in understanding some of the specific genetic causes of this serious psychiatric illness. In particular, several large rare structural variants have been convincingly associated with schizophrenia, in targeted studies over two decades with respect to 22q11.2 microdeletions, and more recently in large-scale, genome-wide case-control studies. These advances promise to help many families afflicted with this disease. In this review, we critically appraise recent developments in the field of schizophrenia genetics through the lens of immediate clinical applicability. Much work remains in translating the recent surge of genetic research discoveries into the clinic. The epidemiology and basic genetic parameters (such as penetrance and expression of most genomic disorders associated with schizophrenia are not yet well characterized. To date, 22q11.2 deletion syndrome is the only established genetic subtype of schizophrenia of proven clinical relevance. We use this well-established association as a model to chart the pathway for translating emerging genetic discoveries into clinical practice. We also propose new directions for research involving general genetic risk prediction and counseling in schizophrenia.Keywords: schizophrenia, genetics, 22q11 deletion syndrome, copy number variation, genetic counseling, genetic predisposition to disease

  5. Genetics Home Reference: Menkes syndrome

    Science.gov (United States)

    ... translocating P-type ATPase (ATP7A): biochemical and cell biology properties, and role in Menkes disease. J Bioenerg Biomembr. 2002 Oct;34(5):363-71. Review. Citation on PubMed de Bie P, Muller P, Wijmenga C, Klomp LW. Molecular pathogenesis of Wilson and Menkes disease: correlation of ...

  6. Utility of Post-Mortem Genetic Testing in Cases of Sudden Arrhythmic Death Syndrome

    NARCIS (Netherlands)

    Lahrouchi, Najim; Raju, Hariharan; Lodder, Elisabeth M.; Papatheodorou, Efstathios; Ware, James S.; Papadakis, Michael; Tadros, Rafik; Cole, Della; Skinner, Jonathan R.; Crawford, Jackie; Love, Donald R.; Pua, Chee J.; Soh, Bee Y.; Bhalshankar, Jaydutt D.; Govind, Risha; Tfelt-Hansen, Jacob; Winkel, Bo G.; van der Werf, Christian; Wijeyeratne, Yanushi D.; Mellor, Greg; Till, Jan; Cohen, Marta C.; Tome-Esteban, Maria; Sharma, Sanjay; Wilde, Arthur A. M.; Cook, Stuart A.; Bezzina, Connie R.; Sheppard, Mary N.; Behr, Elijah R.

    2017-01-01

    Sudden arrhythmic death syndrome (SADS) describes a sudden death with negative autopsy and toxicological analysis. Cardiac genetic disease is a likely etiology. This study investigated the clinical utility and combined yield of post-mortem genetic testing (molecular autopsy) in cases of SADS and

  7. Utility of Post-Mortem Genetic Testing in Cases of Sudden Arrhythmic Death Syndrome

    DEFF Research Database (Denmark)

    Lahrouchi, Najim; Raju, Hariharan; Lodder, Elisabeth M

    2017-01-01

    BACKGROUND: Sudden arrhythmic death syndrome (SADS) describes a sudden death with negative autopsy and toxicological analysis. Cardiac genetic disease is a likely etiology. OBJECTIVES: This study investigated the clinical utility and combined yield of post-mortem genetic testing (molecular autopsy...

  8. Genetic alterations in syndromes with oral manifestations

    Directory of Open Access Journals (Sweden)

    Krishnamurthy Anuthama

    2013-01-01

    Full Text Available Ever since Gregor Johan Mendel proposed the law of inheritance, genetics has transcended the field of health and has entered all walks of life in its application. Thus, the gene is the pivoting factor for all happenings revolving around it. Knowledge of gene mapping in various diseases would be a valuable tool in prenatally diagnosing the condition and averting the future disability and stigma for the posterity. This article includes an array of genetically determined conditions in patients seen at our college out-patient department with complete manifestation, partial manifestation and array of manifestations not fitting into a particular syndrome.

  9. Genetic alterations in syndromes with oral manifestations.

    Science.gov (United States)

    Anuthama, Krishnamurthy; Prasad, Harikrishnan; Ramani, Pratibha; Premkumar, Priya; Natesan, Anuja; Sherlin, Herald J

    2013-11-01

    Ever since Gregor Johan Mendel proposed the law of inheritance, genetics has transcended the field of health and has entered all walks of life in its application. Thus, the gene is the pivoting factor for all happenings revolving around it. Knowledge of gene mapping in various diseases would be a valuable tool in prenatally diagnosing the condition and averting the future disability and stigma for the posterity. This article includes an array of genetically determined conditions in patients seen at our college out-patient department with complete manifestation, partial manifestation and array of manifestations not fitting into a particular syndrome.

  10. Otosclerosis: From Genetics to Molecular Biology.

    Science.gov (United States)

    Babcock, Thomas A; Liu, Xue Zhong

    2018-04-01

    Over the past several years, with the evolution of genetic and molecular research, several etiologic factors have been implicated in the pathogenesis of otosclerosis. Overall, current evidence suggests that otosclerosis is a complex disease with a variety of potential pathways contributing to the development of abnormal bone remodeling in the otic capsule. These pathways involved in the pathogenesis of otosclerosis are influenced by both genetic and environmental factors. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Genetics of childhood steroid-sensitive nephrotic syndrome.

    Science.gov (United States)

    Karp, Alana M; Gbadegesin, Rasheed A

    2016-07-29

    The pathogenesis of childhood-onset nephrotic syndrome (NS), disparity in incidence of NS among races, and variable responses to therapies in children with NS have defied explanation to date. In the last 20 years over 50 genetic causes of steroid-resistant nephrotic syndrome (SRNS) have been identified, and at least two disease loci for two pathologic variants of SRNS (focal segmental glomerulosclerosis and membranous nephropathy) have been defined. However, the genetic causes and risk loci for steroid-sensitive nephrotic syndrome (SSNS) remain elusive, partly because SSNS is relatively rare and also because cases of SSNS vary widely in phenotypic expression over time. A recent study of a well-defined modest cohort of children with SSNS identified variants in HLA-DQA1 as a risk factor for SSNS. Here we review what is currently known about the genetics of SSNS and also discuss how recent careful phenotypic and genomic studies reinforce the role of adaptive immunity in the molecular mechanisms of SSNS.

  12. GENETICS OF CHILDHOOD STEROID SENSITIVE NEPHROTIC SYNDROME (SSNS)

    Science.gov (United States)

    Karp, Alana M.; Gbadegesin, Rasheed A.

    2016-01-01

    The pathogenesis of childhood-onset nephrotic syndrome (NS), disparity in incidence of NS among races, and variable responses to therapies in children with NS have defied explanation to date. In the last twenty years over 50 genetic causes of steroid resistant nephrotic syndrome (SRNS) have been identified and at least two disease loci for two pathologic variants of SRNS (FSGS and membranous nephropathy) have been defined. However, the genetic causes and risk loci for steroid sensitive nephrotic syndrome (SSNS) remain elusive partly because SSNS is relatively rare and also because cases of SSNS vary widely in phenotypic expression over time. A recent study of a well-defined modest cohort of children with SSNS identified variants in HLA-DQA1 as a risk factor for SSNS. This article reviews what is currently known about the genetics of SSNS and also discusses how recent careful phenotypic and genomic studies reinforce the role of adaptive immunity in the molecular mechanisms of SSNS. PMID:27470160

  13. Bacteria, genetics and irritable bowel syndrome.

    LENUS (Irish Health Repository)

    Craig, Orla F

    2010-06-01

    EVALUATION OF: Villani AC, Lemire M, Thabane M et al. Genetic risk factors for post-infectious irritable bowel syndrome following a waterborne outbreak of gastroenteritis. Gastroenterology 138, 1502-1513 (2010). While the pathogenesis of irritable bowel syndrome (IBS) remains to be fully defined, two clinical observations - the occurrence, de novo, of IBS following bacterial gastroenteritis and the history, commonly obtained from IBS patients, of other instances of the syndrome within their families - have instigated investigations, in IBS, of the potential roles, on the one hand, of the gut microbiota and the host response and, on the other hand, of genetic factors. The study reviewed here relates to both of these factors by studying genetic predisposition to postinfective IBS in a large population of individuals who were exposed to a multimicrobial enteric infection, which resulted in a severe outbreak of gastroenteritis and was followed by the development of IBS in over a third. In this detailed study, the investigators identified a number of genes that were linked significantly to the development of postinfectious-IBS in the Toll-like receptor 9, IL-6 and cadherin 1 regions. These genes play important roles in bacterial recognition, the inflammatory response and epithelial integrity, respectively, and provide considerable support for the hypothesis that links IBS onset to disturbances in the microbiota and the host response.

  14. [Colorectal cancer (CCR): genetic and molecular alterations].

    Science.gov (United States)

    Juárez-Vázquez, Clara Ibet; Rosales-Reynoso, Mónica Alejandra

    2014-01-01

    The aim of this review is to present a genetic and molecular overview of colorectal carcinogenesis (sporadic and hereditary origin) as a multistage process, where there are a number of molecular mechanisms associated with the development of colorectal cancer and genomic instability that allows the accumulation of mutations in proto-oncogenes and tumor suppressor genes, chromosomal instability, and methylation and microsatellite instability, and the involvement of altered expression of microRNAs' prognosis factors.

  15. Metabolic Syndrome: Genetic Insights into Disease Pathogenesis

    Science.gov (United States)

    Ziki, Maen D. Abou; Mani, Arya

    2016-01-01

    Purpose of review Metabolic syndrome (MetS) is a cluster of inter-related and heritable metabolic traits, which collectively impart unsurpassed risk for atherosclerotic cardiovascular disease and type 2 diabetes. Considerable work has been done to understand the underlying disease mechanisms by elucidating its genetic etiology. Recent findings Genome-wide association studies (GWAS) have been widely utilized albeit with modest success in identifying variants that are associated with more than two metabolic traits. Another limitation of this approach is the inherent small effect of the common variants, a major barrier for dissecting their cognate pathways. Modest advances in this venue have been also made by genetic studies of kindreds at the extreme ends of quantitative distributions. These efforts have led to the discovery of a number of disease genes with large effects that underlie the association of diverse traits of this syndrome. Summary Substantial progress has been made over the last decade in identification of genetic risk factors associated with the various traits of MetS. The heterogeneity and multifactorial heritability of MetS, however, has been a challenge towards understanding the factors underlying the association of these traits. Genetic investigations of outlier kindreds or homogenous populations with high prevalence for the disease can potentially improve our knowledge of the disease pathophysiology. PMID:26825138

  16. The pediatric nephrotic syndrome spectrum: Clinical homogeneity and molecular heterogeneity

    OpenAIRE

    Schachter, Asher D.

    2004-01-01

    Idiopathic nephrotic syndrome is the most common glomerular disorder of childhood. Recurrence of nephrotic syndrome immediately following renal transplantation is rapid, results in a high rate of graft loss, and represents the most severe form of nephrotic syndrome. This review discusses the molecular heterogeneity of pediatric nephrotic syndrome across the spectrum of disease activity. A schema is offered for a molecular approach to pediatric nephrotic syndrome, including immune-mediated and...

  17. Silver-Russell Syndrome and Beckwith-Wiedemann Syndrome: Opposite Phenotypes with Heterogeneous Molecular Etiology

    Science.gov (United States)

    Õunap, Katrin

    2016-01-01

    Silver-Russell syndrome (SRS) and Beckwith-Wiedemann syndrome (BWS) are 2 clinically opposite growth-affecting disorders belonging to the group of congenital imprinting disorders. The expression of both syndromes usually depends on the parental origin of the chromosome in which the imprinted genes reside. SRS is characterized by severe intrauterine and postnatal growth retardation with various additional clinical features such as hemihypertrophy, relative macrocephaly, fifth finger clinodactyly, and triangular facies. BWS is an overgrowth syndrome with many additional clinical features such as macroglossia, organomegaly, and an increased risk of childhood tumors. Both SRS and BWS are clinically and genetically heterogeneous, and for clinical diagnosis, different diagnostic scoring systems have been developed. Six diagnostic scoring systems for SRS and 4 for BWS have been previously published. However, neither syndrome has common consensus diagnostic criteria yet. Most cases of SRS and BWS are associated with opposite epigenetic or genetic abnormalities in the 11p15 chromosomal region leading to opposite imbalances in the expression of imprinted genes. SRS is also caused by maternal uniparental disomy 7, which is usually identified in 5-10% of the cases, and is therefore the first imprinting disorder that affects 2 different chromosomes. In this review, we describe in detail the clinical diagnostic criteria and scoring systems as well as molecular causes in both SRS and BWS. PMID:27587987

  18. Molecular species identification and population genetics of ...

    African Journals Online (AJOL)

    Molecular genetic techniques, such as DNA barcoding and genotyping, are increasingly being used to assist with the conservation and management of chondrichthyans worldwide. Southern Africa is a shark biodiversity hotspot, with a large number of endemic species. According to the IUCN Red List, a quarter of South ...

  19. A molecular genetic toolbox for Yarrowia lipolytica

    DEFF Research Database (Denmark)

    Bredeweg, Erin L.; Pomraning, Kyle R.; Dai, Ziyu

    2017-01-01

    used these tools to build the "Yarrowia lipolytica Cell Atlas," a collection of strains with endogenous fluorescently tagged organelles in the same genetic background, in order to define organelle morphology in live cells. Conclusions: These molecular and isogenetic tools are useful for live assessment...

  20. Molecular diversity and genetic relationships in Secale

    Indian Academy of Sciences (India)

    The objective of this study was to quantify the molecular diversity and to determine the genetic relationships amongSecalespp. and among cultivars ofSecale ... Faculty of Sciences, Campo Grande, Lisboa, Portugal; Departamento de Genética, Facultad de Biologia, Universidad Complutense, C/ José Antonio Novais, 12, ...

  1. Molecular genetics in affective illness

    Energy Technology Data Exchange (ETDEWEB)

    Mendlewicz, J.; Sevy, S.; Mendelbaum, K. (Erasme Univ. Hospital, Brussels (Belgium))

    1993-01-01

    Genetic transmission in manic depressive illness (MDI) has been explored in twins, adoption, association, and linkage studies. The X-linked transmission hypothesis has been tested by using several markers on chromosome X: Xg blood group, color blindness, glucose-6-phosphate dehydrogenase (G6PD), factor IX (hemophilia B), and DNA probes such as DXS15, DXS52, F8C, ST14. The hypothesis of autosomal transmission has been tested by association studies with the O blood group located on chromosome 9, as well as linkage studies on chromosome 6 with the Human Leucocyte Antigens (HLA) haplotypes and on Chromosome 11 with DNA markers for the following genes: D2 dopamine receptor, tyrosinase, C-Harvey-Ras-A (HRAS) oncogene, insuline (ins), and tyrosine hydroxylase (TH). Although linkage studies support the hypothesis of a major locus for the transmission of MDI in the Xq27-28 region, several factors are limiting the results, and are discussed in the present review. 105 refs., 1 fig., 2 tabs.

  2. Molecular genetics of dyslexia: an overview.

    Science.gov (United States)

    Carrion-Castillo, Amaia; Franke, Barbara; Fisher, Simon E

    2013-11-01

    Dyslexia is a highly heritable learning disorder with a complex underlying genetic architecture. Over the past decade, researchers have pinpointed a number of candidate genes that may contribute to dyslexia susceptibility. Here, we provide an overview of the state of the art, describing how studies have moved from mapping potential risk loci, through identification of associated gene variants, to characterization of gene function in cellular and animal model systems. Work thus far has highlighted some intriguing mechanistic pathways, such as neuronal migration, axon guidance, and ciliary biology, but it is clear that we still have much to learn about the molecular networks that are involved. We end the review by highlighting the past, present, and future contributions of the Dutch Dyslexia Programme to studies of genetic factors. In particular, we emphasize the importance of relating genetic information to intermediate neurobiological measures, as well as the value of incorporating longitudinal and developmental data into molecular designs. Copyright © 2013 John Wiley & Sons, Ltd.

  3. [Molecular basis of Rett syndrome: A current look].

    Science.gov (United States)

    Pantaleón F, Gretta; Juvier R, Tamara

    2015-01-01

    Rett syndrome (RS) is a neurodevelopmental disorder that exclusively affects girls, and occurs along with autism. It is very uncommon, and has five distinct forms, one classic and the others atypical, which generally compromise manual skills, language, and mobility, and widely associated with the appearance of stereotypy and early epilepsy. With the aim of updating the information about RS, a search was performed in the computer data bases of PubMed, Hinari, SCIELO and Medline, as well as consulting other web sites including OMIM, ORPHANET, GeneMap, Genetests, Proteins and Gene, using the descriptors "Síndrome de Rett", "genes y Síndrome de Rett", "Rett Syndrome gene", "Rett Syndrome", "Rett Syndrome gene therapy", and "Rett Syndrome review". Of the 1,348 articles found, 42 articles were selected, which reported 3 genes causing the syndrome: MECP2, CDKL5 and FOXG. The MECP2 gene is mutated in 80% of patients with classic RS, as well as in 40% of those affected by any of its atypical forms. RS with early epilepsy and the congenital variant are mainly due to variations in the CDKL5 and FOXG1 genes, respectively. The diagnosis of RS is based on clinical criteria. However, the advances in molecular biology and genetics have opened a wide range of possibilities for diagnosing the different clinical forms that could not be classified before. Molecular analysis can help confirm the clinical criteria and provided information as regards the prognosis of the patient. Copyright © 2015. Publicado por Elsevier España, S.L.U.

  4. [Genetics of cryopyrin-associated periodic syndrome].

    Science.gov (United States)

    Kümmerle-Deschner, J B; Lohse, P

    2017-05-01

    Familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and chronic infantile neurological, cutaneous and articular syndrome/neonatal onset multisystem inflammatory disease (CINCA/NOMID) were originally described as three distinct diseases. After the identification of their common genetic origin in 2001 and 2002, they are now perceived as a continuum of one disease entity and labelled cryopyrin-associated periodic syndromes (CAPS). Mutations in the NLRP3 gene on chromosome 1q44 can be detected in many affected patients. These lead to the synthesis of an altered gene product named cryopyrin. This is part of the NLRP3 inflammasome and causes the activation of caspase 1 and an excess production of IL-1β, which is the driving force behind the inflammatory reactions observed in CAPS patients. In symptomatic patients, confirmation of a mutation using traditional methods of genetic analysis may not always be successful (up to 40% in the case of CINCA/NOMID phenotypes); however, in many cases somatic mutations can be found using modern methods, such as next generation sequencing (NGS) technologies. In contrast, low-penetrance NLRP3 variants may also be identified in healthy family members and are present in low frequencies in the general population. Some of the mutation carriers nevertheless present with typical signs of autoinflammation; however, their phenotype is different compared to the classical CAPS presentation. These patients display unspecific systemic inflammatory signs more frequently but show an organ involvement less often. While the detection of NLRP3 gene mutations may be viewed as confirmatory, CAPS is still predominantly a clinical diagnosis; therefore, recently published diagnostic criteria do not require the demonstration of a mutation.

  5. INHERITED PATHOLOGY OF β2-LAMININ (PIERSON SYNDROME: CLINICAL AND GENETIC ASPECTS

    Directory of Open Access Journals (Sweden)

    M.Yu. Kagan

    2010-01-01

    Full Text Available For the last decade a great successes were attained in the study of molecular bases of glomerular diseases. It was certain that the most frequent reasons of congenital and infantile nephrotic syndrome are mutations in the genes of NPHS1, NPHS2, and WT1. Nevertheless, until now, a number of patients, having combination of early nephrotic syndrome with inherent pathology of other organs, which etiology remains un known. These cases continue to be intensively probed. One of the most important recent achievements in understanding of molecular mechanisms of early nephrotic syndrome is the discovery of mutations of gene of LAMB2, encoding β2 laminin, as the cause of Pearson syndrome (OMIM#609049. In this article the author presents the basic genetic and clinical descriptions of this recently identified pathology. Key words: Pearson syndrome, congenital nephrotic syndrome, β2 laminin, malformation of organ of vision. (Pediatric Pharmacology. – 2010; 7(3:114-117

  6. Brachmann-Cornelia de Lange syndrome with a papilloma of the choroid plexus: analyses of molecular genetic characteristics of the patient and the tumor. A single-case study.

    Science.gov (United States)

    de León, Fernando Chico-Ponce; Gordillo-Domínguez, Luis F; González-Carranza, Vicente; Torres-García, Samuel; García-Delgado, Constanza; Sánchez-Boiso, Adriana; Arenas-Huertero, Francisco; Perezpeña-Diazconti, Mario; Eguía-Aguilar, Pilar; Baqueiro-Hernández, César; Buenrostro-Márquez, Guillermo; Martínez-Rodríguez, Sonia; Dhellemmes, Patrick; Castro-Sierra, Eduardo

    2015-01-01

    A 10-month-old girl with a Brachmann-Cornelia de Lange syndrome and a choroid plexus papilloma of the brain was studied at the Hospital Infantil de México Federico Gómez (HIMFG) in Mexico City. Presumptive papilloma of the third ventricle was evidenced on CT and MR images and removed. Pathological analysis confirmed its origin. A posterior radiosurgery was required due to a tumor relapse. Karyotypes (GTG bands) of the patient and her parents undertaken at HIMFG were normal. Array comparative genomic hybridization (array CGH) analyses of blood DNA of the patient and her parents carried out at BlueGnome's Laboratory in Cambridge, UK, set in evidence amplification of genes SPNS2, GGT6, SMTNL2, PELP1, MYBBP1A, and ALOX15 in chromosome 17p of the patient. Since MYBBP1A is a proto-oncogene and ALOX15 participates in the development of cancer and metastases of tumors, further fluorescent in situ hybridization (FISH) analyses of these two genes were implemented at HIMFG. Amplification of the two genes was found in the tumor of the case under study but not in an unrelated papilloma of the choroid plexus. Further analyses of the association of choroid plexus papillomas with disorders of psycho-neural development and its relationship to molecular genetic modifications at chromosome 17p are now under way at HIMFG.

  7. Cytomegalovirus infection can mimic genetic nephrotic syndrome: a case report.

    Science.gov (United States)

    Hogan, Julien; Fila, Marc; Baudouin, Véronique; Peuchmaur, Michel; Deschênes, Georges; Niel, Olivier

    2015-09-22

    Nephrotic syndrome is a relatively rare but serious condition in children. Infantile nephrotic syndrome often has a genetic origin; the treatment is then symptomatic, with a poor prognosis, and a rapid evolution to chronic kidney disease. However, non-genetic infantile nephrotic syndrome has been identified. Here we report for the first time in a child a nephrotic syndrome as the sole clinical expression of a cytomegalovirus infection. The patient was 5 months old when he presented with a nephrotic syndrome. An exhaustive genetic testing was conducted and came back negative. A viral work-up only showed a positive cytomegalovirus PCR. Antiviral treatment lead to a complete remission of the nephrotic syndrome, with no requirement for steroid therapy. Renal function remained normal throughout follow-up. Nephrotic syndrome should always be carefully investigated in children. This observation reinforces the connection between viral infections and pediatric nephrotic syndrome, sparking more controversy about an infectious origin to childhood nephrotic disease.

  8. Genetic neurological channelopathies: molecular genetics and clinical phenotypes.

    Science.gov (United States)

    Spillane, J; Kullmann, D M; Hanna, M G

    2016-01-01

    Evidence accumulated over recent years has shown that genetic neurological channelopathies can cause many different neurological diseases. Presentations relating to the brain, spinal cord, peripheral nerve or muscle mean that channelopathies can impact on almost any area of neurological practice. Typically, neurological channelopathies are inherited in an autosomal dominant fashion and cause paroxysmal disturbances of neurological function, although the impairment of function can become fixed with time. These disorders are individually rare, but an accurate diagnosis is important as it has genetic counselling and often treatment implications. Furthermore, the study of less common ion channel mutation-related diseases has increased our understanding of pathomechanisms that is relevant to common neurological diseases such as migraine and epilepsy. Here, we review the molecular genetic and clinical features of inherited neurological channelopathies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  9. Current developments in the genetics of Rett and Rett-like syndrome.

    Science.gov (United States)

    Ehrhart, Friederike; Sangani, Nasim B; Curfs, Leopold M G

    2018-03-01

    This article reviews the current molecular genetic studies, which investigate the genetic causes of Rett syndrome or Rett-like phenotypes without a MECP2 mutation. As next generation sequencing becomes broadly available, especially whole exome sequencing is used in clinical diagnosis of the genetic causes of a wide spectrum of intellectual disability, autism, and encephalopathies. Patients who were diagnosed with Rett syndrome or Rett-like syndrome because of their phenotype but were negative for mutations in the MECP2, CDKL5 or FOXG1 genes were subjected to whole exome sequencing and the results of the last few years revealed yet 69 different genes. Many of these genes are involved in epigenetic gene regulation, chromatin shaping, neurotransmitter action or RNA transcription/translation. Genetic data also allows to investigate the individual genetic background of an individual patient, which can modify the severity of a genetic disorder. We conclude that the Rett syndrome phenotype has a much broader underlying genetic cause and the typical phenotype overlap with other genetic disorders. For proper genetic counselling, patient perspective and treatment it is important to include both phenotype and genetic information.

  10. The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism

    Science.gov (United States)

    Bianco, Suzy D. C.; Kaiser, Ursula B.

    2010-01-01

    Idiopathic hypogonadotropic hypogonadism (IHH) has an incidence of 1–10 cases per 100,000 births. About 60% of patients with IHH present with associated anosmia, also known as Kallmann syndrome, characterized by total or partial loss of olfaction. Many of the gene mutations associated with Kallmann syndrome have been mapped to KAL1 or FGFR1. However, together, these mutations account for only about 15% of Kallmann syndrome cases. More recently, mutations in PROK2 and PROKR2 have been linked to the syndrome and may account for an additional 5–10% of cases. The remaining 40% of patients with IHH have a normal sense of smell. Prior to 2003, the only gene linked to normosmic IHH was the gonadotropin-releasing hormone receptor gene. However, mutations in this receptor are believed to account for only 10% of cases. Subsequently, mutations in KISS1R, TAC3 and TACR3 were identified as causes of normosmic IHH. Certain genes, including PROK2 and FGFR1, are associated with both anosmic and normosmic IHH. Despite recent advances in the field, the genetic causes of the majority of cases of IHH remain unknown. This Review discusses genes associated with hypogonadotropic disorders and the molecular mechanisms by which mutations in these genes may result in IHH. PMID:19707180

  11. Genetics Home Reference: mosaic variegated aneuploidy syndrome

    Science.gov (United States)

    ... they typically have an unusually small head size ( microcephaly ). Another common feature of MVA syndrome is an ... Other Names for This Condition mosaic variegated aneuplody microcephaly syndrome MVA syndrome Warburton-Anyane-Yeboa syndrome Related ...

  12. Analysis of Downs syndrome with molecular techniques for future diagnoses

    Directory of Open Access Journals (Sweden)

    May Salem Al-Nbaheen

    2018-03-01

    Full Text Available Down syndrome (DS is a genetic disorder appeared due to the presence of trisomy in chromosome 21 in the G-group of the acrocentric region. DS is also known as non-Mendelian inheritance, due to the lack of Mendel’s laws. The disorder in children is identified through clinical symptoms and chromosomal analysis and till now there are no biochemical and molecular analyses. Presently, whole exome sequencing (WES has largely contributed in identifying the new disease-causing genes and represented a significant breakthrough in the field of human genetics and this technique uses high throughput sequencing technologies to determine the arrangement of DNA base pairs specifying the protein coding regions of an individual’s genome. Apart from this next generation sequencing and whole genome sequencing also contribute for identifying the disease marker. From this review, the suggestion was to perform the WES is DS children to identify the marker region. Keywords: Downs syndrome, Exome sequencing, Chromosomal analysis, Genes, Genetics

  13. Supporting Children with Genetic Syndromes in the Classroom: The Example of 22q Deletion Syndrome

    Science.gov (United States)

    Reilly, Colin; Stedman, Lindsey

    2013-01-01

    An increasing number of children are likely to have a known genetic cause for their special educational needs. One such genetic condition is 22q11.2 deletion syndrome (22qDS), a genetic syndrome associated with early speech and language difficulties, global and specific cognitive impairments, difficulties with attention and difficulties with…

  14. Genetic Determinants of Non-syndromic Hearing Impairment

    NARCIS (Netherlands)

    R.L.P. Santos (Regie)

    2006-01-01

    textabstractCongenital hearing impairment (HI) affects 1-2 per 1000 neonates, of which half would be genetic in etiology. Of the genetic cases, 70% would be non-syndromic in nature. To date ~120 non-syndromic (NS) HI loci have been mapped, for which 39 NSHI genes have been identified. For the

  15. Klinefelter syndrome - integrating genetics, neuropsychology and endocrinology.

    Science.gov (United States)

    Gravholt, Claus H; Chang, Simon; Wallentin, Mikkel; Fedder, Jens; Moore, Philip; Skakkebæk, Anne

    2018-02-09

    Although first identified over 70 years ago, Klinefelter syndrome (KS) continue to pose significant diagnostic challenges, as many patients are still misdiagnosed, or remain undiagnosed. In fact, as few as 25% of KS patients are accurately diagnosed, and most of these diagnoses are not made until adulthood. Classic characteristics of KS include small testes, infertility, hypergonadothropic hypogonadism, and cognitive impairment. However, the pathophysiology behind KS is not well understood, although genetic effects are also thought to play a role. For example, recent developments in genetics and genomics point to a fundamental change in our understanding of KS, with global epigenetic and RNA expression changes playing a central role for the phenotype.KS is also associated with more general health markers, including higher morbidity and mortality rates, and lower socio-economic status (which likely affects both morbidity and mortality). In addition, hypogonadism is associated with greater risk of of metabolic syndrome, type 2 diabetes, cardiovascular disease, breast cancer, and extragonadal germ cell tumors. Medical treatment typically focuses on testosterone replacement therapy (TRT), although the effects of this therapy has not been studied rigorously, and future studies need to evaluate the effects of TRT on metabolic risk and neurocognitive outcomes.This review presents a comprehensive, interdisciplinary examination of recent developments in genetic, endocrine and neurocognitive science, including the study of animal models regarding KS. It also provides a number of recommendations for improving the effectiveness of research and clinical practice, including neonatal KS screening programs, and a multidisciplinary approach to KS treatment from childhood until senescence. Copyright © 2018 Endocrine Society.

  16. Molecular Genetic of Atopic dermatitis: An Update

    Science.gov (United States)

    Al-Shobaili, Hani A.; Ahmed, Ahmed A.; Alnomair, Naief; Alobead, Zeiad Abdulaziz; Rasheed, Zafar

    2016-01-01

    Atopic dermatitis (AD) is a chronic multifactorial inflammatory skin disease. The pathogenesis of AD remains unclear, but the disease results from dysfunctions of skin barrier and immune response, where both genetic and environmental factors play a key role. Recent studies demonstrate the substantial evidences that show a strong genetic association with AD. As for example, AD patients have a positive family history and have a concordance rate in twins. Moreover, several candidate genes have now been suspected that play a central role in the genetic background of AD. In last decade advanced procedures similar to genome-wide association (GWA) and single nucleotide polymorphism (SNP) have been applied on different population and now it has been clarified that AD is significantly associated with genes of innate/adaptive immune systems, human leukocyte antigens (HLA), cytokines, chemokines, drug-metabolizing genes or various other genes. In this review, we will highlight the recent advancements in the molecular genetics of AD, especially on possible functional relevance of genetic variants discovered to date. PMID:27004062

  17. Challenging behavior: Behavioral phenotypes of some genetic syndromes

    Directory of Open Access Journals (Sweden)

    Buha Nataša

    2014-01-01

    Full Text Available Challenging behavior in individuals with mental retardation (MR is relatively frequent, and represents a significant obstacle to adaptive skills. The frequency of specific forms and manifestations of challenging behavior can depend on a variety of personal and environmental factors. There are several prominent theoretical models regarding the etiology of challenging behavior and psychopathology in persons with MR: behavioral, developmental, socio-cultural and biological. The biological model emphasizes the physiological, biochemical and genetic factors as the potential source of challenging behavior. The progress in the field of genetics and neuroscience has opened the opportunity to study and discover the neurobiological basis of phenotypic characteristics. Genetic syndromes associated with MR can be followed by a specific set of problems and disorders which constitutes their behavioral phenotype. The aim of this paper was to present challenging behaviors that manifest in the most frequently studied syndromes: Down syndrome, Fragile X syndrome, Williams syndrome, Prader-Willi syndrome and Angelman syndrome. The concept of behavioral phenotype implies a higher probability of manifesting specific developmental characteristics and specific behaviors in individuals with a certain genetic syndrome. Although the specific set of (possible problems and disorders is distinctive for the described genetic syndromes, the connection between genetics and behavior should be viewed through probabilistic dimension. The probabilistic concept takes into consideration the possibility of intra-syndrome variability in the occurrence, intensity and time onset of behavioral characteristics, at which the higher variability the lower is the specificity of the genetic syndrome. Identifying the specific pattern of behavior can be most important for the process of early diagnosis and prognosis. In addition, having knowledge about behavioral phenotype can be a landmark in

  18. [22q11.2DS Syndrome as a Genetic Subtype of Schizophrenia].

    Science.gov (United States)

    Huertas-Rodríguez, Cindy Katherin; Payán-Gómez, César; Forero-Castro, Ruth Maribel

    2015-01-01

    The 22q11.2 deletion syndrome (22q11.2DS) is associated with the microdeletion of this chromosomal region, and represents the second most common genetic syndrome after Down's syndrome. In patients with schizophrenia, 22q11.2DS has a prevalence of 2%, and in selected groups can be increased to between 32-53%. To describe the generalities of 22q11.2DS syndrome as a genetic subtype of schizophrenia, its clinical characteristics, molecular genetic aspects, and frequency in different populations. A review was performed from 1967 to 2013 in scientific databases, compiling articles about 22q11.2DS syndrome and its association with schizophrenia. The 22q11.2 DS syndrome has a variable phenotype associated with other genetic syndromes, birth defects in many tissues and organs, and a high rate of psychiatric disorders, particularly schizophrenia. Likewise, it has been identified in clinical populations with schizophrenia selected by the presence of common syndromic characteristics. FISH, qPCR and MLPA techniques, and recently, aCGH and NGS technologies, are being used to diagnose this microdeletion. It is important in clinical practice to remember that people suffering the 22q11.2DS have a high genetic risk for developing schizophrenia, and it is considered that the simultaneous presence of this disease and 22q11.2DS represents a genetic subtype of schizophrenia. There are clear phenotypic criteria, molecular and cytogenetic methods to diagnose this group of patients, and to optimize a multidisciplinary approach in their monitoring. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  19. Molecular Genetic Markers in Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Sophia Yohe

    2015-03-01

    Full Text Available Genetics play an increasingly important role in the risk stratification and management of acute myeloid leukemia (AML patients. Traditionally, AML classification and risk stratification relied on cytogenetic studies; however, molecular detection of gene mutations is playing an increasingly important role in classification, risk stratification, and management of AML. Molecular testing does not take the place of cytogenetic testing results, but plays a complementary role to help refine prognosis, especially within specific AML subgroups. With the exception of acute promyelocytic leukemia, AML therapy is not targeted but the intensity of therapy is driven by the prognostic subgroup. Many prognostic scoring systems classify patients into favorable, poor, or intermediate prognostic subgroups based on clinical and genetic features. Current standard of care combines cytogenetic results with targeted testing for mutations in FLT3, NPM1, CEBPA, and KIT to determine the prognostic subgroup. Other gene mutations have also been demonstrated to predict prognosis and may play a role in future risk stratification, although some of these have not been confirmed in multiple studies or established as standard of care. This paper will review the contribution of cytogenetic results to prognosis in AML and then will focus on molecular mutations that have a prognostic or possible therapeutic impact.

  20. Restless legs syndrome in Czech patients with multiple sclerosis: An epidemiological and genetic study

    Czech Academy of Sciences Publication Activity Database

    Vávrová, J.; Kemlink, D.; Šonka, K.; Havrdová, E.; Horáková, D.; Pardini, Barbara; Müller-Myhsok, B.; Winkelmann, J.

    2012-01-01

    Roč. 13, č. 7 (2012), s. 848-851 ISSN 1389-9457 R&D Projects: GA MZd NR8563 Grant - others:GA ČR(CZ) GD309/08/H079; GA MZd(CZ) NT12141 Institutional research plan: CEZ:AV0Z50390512 Keywords : Secondary restless legs syndrome * Multiple sclerosis * Genetic association study Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.487, year: 2012

  1. Molecular and genetic mechanisms of environmental mutagens

    International Nuclear Information System (INIS)

    Kubitschek, H.E.; Derstine, P.L.; Griego, V.M.; Matsushita, T.; Peak, J.G.; Peak, M.J.; Reynolds, P.R.; Webb, R.B.; Williams-Hill, D.

    1981-01-01

    This program is primarily concerned with elucidation of the nature of DNA lesions produced by environmental and energy related mutagens, their mechanisms of action, and their repair. The main focus is on actions of chemical mutagens and electromagnetic radiations. Synergistic interactions between mutagens and the mutational processes that lead to synergism are being investigated. Mutagens are chosen for study on the basis of their potential for analysis of mutation (as genetic probes), for development of procedures for reducing mutational damage, for their potential importance to risk assessment, and for development of improved mutagen testing systems. Bacterial cells are used because of the rapidity and clarity of scientific results that can be obtained, the detailed genetic maps, and the many well-defined mutand strains available. The conventional tools of microbial and molecular genetics are used, along with intercomparison of genetically related strains. Advantage is taken of tcollective dose commitment will result in more attention being paid to potential releases of radionuclides at relatively short times after disposal

  2. Present status of understanding on the genetic etiology of polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Dasgupta S

    2008-01-01

    Full Text Available Polycystic ovary syndrome (PCOS is the most common endocrinopathy in women of reproductive age with a prevalence of approximately 7-10% worldwide. PCOS reflects multiple potential aetiologies and variable clinical manifestations. This syndrome is characterized by serious health implications such as diabetes, coronary heart diseases and cancer and also leads to infertility. PCOS can be viewed as a heterogeneous androgen excess disorder with varying degrees of reproductive and metabolic abnormalities determined by the interaction of multiple genetic and environmental factors. In this paper, we have attempted a comprehensive review of primarily molecular genetic studies done so far on PCOS. We have also covered the studies focusing on the environmental factors and impact of ethnicity on the presentation of this syndrome. A large number of studies have been attempted to understand the aetiological mechanisms behind PCOS both at the clinical and molecular genetic levels. In the Indian context, majority of the PCOS studies have been confined to the clinical dimensions. However, a concrete genetic mechanism behind the manifestation of PCOS is yet to be ascertained. Understanding of this complex disorder requires comprehensive studies incorporating relatively larger homogenous samples for genetic analysis and taking into account the ethnicity and the environmental conditions of the population/cohort under study. Research focused on these aspects may provide better understanding on the genetic etiology and the interaction between genes and environment, which may help develop new treatment methods and possible prevention of the syndrome.

  3. Genetics Home Reference: 48,XXYY syndrome

    Science.gov (United States)

    ... and 49,XXXXY syndromes: not just variants of Klinefelter syndrome. Acta Paediatr. 2011 Jun;100(6):851-60. ... on PubMed Central Visootsak J, Graham JM Jr. Klinefelter syndrome and other sex chromosomal aneuploidies. Orphanet J Rare ...

  4. Genetics Home Reference: Bowen-Conradi syndrome

    Science.gov (United States)

    ... Facebook Twitter Home Health Conditions Bowen-Conradi syndrome Bowen-Conradi syndrome Printable PDF Open All Close All ... Javascript to view the expand/collapse boxes. Description Bowen-Conradi syndrome is a disorder that affects many ...

  5. Genetics Home Reference: Coffin-Siris syndrome

    Science.gov (United States)

    ... Facebook Twitter Home Health Conditions Coffin-Siris syndrome Coffin-Siris syndrome Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Coffin-Siris syndrome is a condition that affects several body ...

  6. Genetics Home Reference: dopamine transporter deficiency syndrome

    Science.gov (United States)

    ... Twitter Home Health Conditions Dopamine transporter deficiency syndrome Dopamine transporter deficiency syndrome Printable PDF Open All Close ... Javascript to view the expand/collapse boxes. Description Dopamine transporter deficiency syndrome is a rare movement disorder. ...

  7. Genetics Home Reference: polycystic ovary syndrome

    Science.gov (United States)

    ... Share: Email Facebook Twitter Home Health Conditions Polycystic ovary syndrome Polycystic ovary syndrome Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Polycystic ovary syndrome is a condition that affects women in ...

  8. Genetics Home Reference: Schwartz-Jampel syndrome

    Science.gov (United States)

    ... Facebook Twitter Home Health Conditions Schwartz-Jampel syndrome Schwartz-Jampel syndrome Printable PDF Open All Close All ... Javascript to view the expand/collapse boxes. Description Schwartz-Jampel syndrome is a rare condition characterized by ...

  9. Psychobiology and molecular genetics of resilience.

    Science.gov (United States)

    Feder, Adriana; Nestler, Eric J; Charney, Dennis S

    2009-06-01

    Every individual experiences stressful life events. In some cases acute or chronic stress leads to depression and other psychiatric disorders, but most people are resilient to such effects. Recent research has begun to identify the environmental, genetic, epigenetic and neural mechanisms that underlie resilience, and has shown that resilience is mediated by adaptive changes in several neural circuits involving numerous neurotransmitter and molecular pathways. These changes shape the functioning of the neural circuits that regulate reward, fear, emotion reactivity and social behaviour, which together are thought to mediate successful coping with stress.

  10. Genetics and molecular biology of hypotension

    Science.gov (United States)

    Robertson, D.

    1994-01-01

    Major strides in the molecular biology of essential hypertension are currently underway. This has tended to obscure the fact that a number of inherited disorders associated with low blood pressure exist and that these diseases may have milder and underrecognized phenotypes that contribute importantly to blood pressure variation in the general population. This review highlights some of the gene products that, if abnormal, could cause hypotension in some individuals. Diseases due to abnormalities in the catecholamine enzymes are discussed in detail. It is likely that genetic abnormalities with hypotensive phenotypes will be as interesting and diverse as those that give rise to hypertensive disorders.

  11. [Trichorhinophalangeal syndrome--clinical presentation and genetics].

    Science.gov (United States)

    Brodwall, Kristoffer M; Júlíusson, Pétur B; Bjerknes, Robert; Hovland, Randi; Fiskerstrand, Torunn

    2011-08-09

    The trichorhinophalangeal syndrome (TRPS) is a hereditary, skeletal dysplasia which has a characteristic clinical presentation and is classified in types 1, 2 and 3, based on phenotype and genotype. Typical findings may be mild and many patients probably remain undiagnosed. The paper is based on four case reports and provides a short review of the condition. Our four patients all have typical facial features, such as a large nose and thin upper lip, thin hair and short curved fingers with characteristic radiological findings. The condition is autosomal dominant and caused by a mutation in the TRPS1 gene, which codes a gene-regulating protein involved in development of hair and modulation of chondrocytes. The diagnosis can be based on clinical findings, but DNA-analysis can be of help in unclear situations. Two of our patients were diagnosed from clinical and radiological findings, but for the two others genetic examinations were done as well. There is no causal treatment, but the diagnosis can give patients an explanation of their problems, and genetic counseling for the patient and family can be offered. Orthopedic surgery and cosmetic aids are valuable for many. In an increasingly technified medical daily life, the clinical view is still the most important tool in diagnosing patients with this condition.

  12. Uncoding the genetic heterogeneity of myelodysplastic syndrome.

    Science.gov (United States)

    Lindsley, R Coleman

    2017-12-08

    Myelodysplastic syndrome (MDS) is a clinically heterogeneous disease characterized by functional impairment of hematopoiesis and abnormal bone marrow morphology. The type and severity of hematopoietic dysfunction in MDS are highly variable, and the kinetics of disease progression are difficult to predict. Genomic studies have shown that MDS is typically driven by a multistep somatic genetic process affecting a core set of genes. By definition, recurrent MDS driver mutations all drive clonal dominance, although they can have stereotyped positions in the clonal hierarchy or patterns of comutation association and exclusivity. Furthermore, environmental context, such as exposures to cytotoxic chemotherapy or the presence of germ-line predisposition, can influence disease pathogenesis and clinical outcomes. This review will address how an enhanced understanding of MDS genetics may enable refinement of current diagnostic schema, improve understanding of the pathogenesis of therapy-related MDS, and identify germ-line predispositions to development of MDS that are more common than recognized by standard clinical evaluation. © 2016 by The American Society of Hematology. All rights reserved.

  13. Genetics Home Reference: Björnstad syndrome

    Science.gov (United States)

    ... prevalence is unknown. It has been found in populations worldwide. Related Information What information about a genetic condition can statistics provide? Why are some genetic conditions more common in particular ethnic groups? Genetic Changes Björnstad syndrome is caused by mutations in the ...

  14. Novel Implications in Molecular Diagnosis of Lynch Syndrome

    Directory of Open Access Journals (Sweden)

    Raffaella Liccardo

    2017-01-01

    Full Text Available About 10% of total colorectal cancers are associated with known Mendelian inheritance, as Familial Adenomatous Polyposis (FAP and Lynch syndrome (LS. In these cancer types the clinical manifestations of disease are due to mutations in high-risk alleles, with a penetrance at least of 70%. The LS is associated with germline mutations in the DNA mismatch repair (MMR genes. However, the mutation detection analysis of these genes does not always provide informative results for genetic counseling of LS patients. Very often, the molecular analysis reveals the presence of variants of unknown significance (VUSs whose interpretation is not easy and requires the combination of different analytical strategies to get a proper assessment of their pathogenicity. In some cases, these VUSs may make a more substantial overall contribution to cancer risk than the well-assessed severe Mendelian variants. Moreover, it could also be possible that the simultaneous presence of these genetic variants in several MMR genes that behave as low risk alleles might contribute in a cooperative manner to increase the risk of hereditary cancer. In this paper, through a review of the recent literature, we have speculated a novel inheritance model in the Lynch syndrome; this could pave the way toward new diagnostic perspectives.

  15. Strengthening molecular genetics and training in craniosynostosis: The need of the hour

    Directory of Open Access Journals (Sweden)

    Mayadhar Barik

    2014-01-01

    Full Text Available Craniosynostosis (CS is premature fusion of skull. It is divided into two groups: Syndromic craniosynostosis (SCS and non-syndromic craniosynostosis (NSC. Its incidence in Indian population is 1:1000 live births where as in the USA it is 1:2500 live births. Its incidence varies from country to country. Molecular genetics having great interest and relevance in medical students, faculty, scientist, pediatric neurosurgeon and staff nurses, our objective was to educate the medical students, residents, researchers, clinicians, pediatric neurosurgeon, anesthetists, pediatricians, staff nurses and paramedics. We summarized here including with diagnosis, investigations, surgical therapy, induction therapy, and molecular therapy. Molecular genetics training is needed to know the information regarding development of skull, cranial connective tissue, craniofacial dysplasia, frame work, network of receptors and its etiopathogenesis. The important part is clinically with molecular therapy (MT how to manage CS in rural sector and metropolitan cities need a special attention.

  16. Molecular and Cellular Mechanisms Elucidating Neurocognitive Basis of Functional Impairments Associated with Intellectual Disability in Down Syndrome

    Science.gov (United States)

    Rachidi, Mohammed; Lopes, Carmela

    2010-01-01

    Down syndrome, the most common genetic cause of intellectual disability, is associated with brain disorders due to chromosome 21 gene overdosage. Molecular and cellular mechanisms involved in the neuromorphological alterations and cognitive impairments are reported herein in a global model. Recent advances in Down syndrome research have lead to…

  17. Unmet Needs in Dystonia: Genetics and Molecular Biology-How Many Dystonias?

    Science.gov (United States)

    Verbeek, Dineke S; Gasser, Thomas

    2016-01-01

    Genetic findings of the past years have provided ample evidence for a substantial etiologic heterogeneity of dystonic syndromes. While an increasing number of genes are being identified for Mendelian forms of isolated and combined dystonias using classical genetic mapping and whole-exome sequencing techniques, their precise role in the molecular pathogenesis is still largely unknown. Also, the role of genetic risk factors in the etiology of sporadic dystonias is still enigmatic. Only the systematic ascertainment and precise clinical characterization of very large cohorts with dystonia, combined with systematic genetic studies, will be able to unravel the complex network of factors that determine disease risk and phenotypic expression.

  18. Genetic Testing in Acute Myeloid Leukemia and Myelodysplastic Syndromes.

    Science.gov (United States)

    Nardi, Valentina; Hasserjian, Robert P

    2016-03-01

    Cytogenetic analysis of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) is essential for disease diagnosis, classification, prognostic stratification, and treatment guidance. Molecular genetic analysis of CEBPA, NPM1, and FLT3 is already standard of care in patients with AML, and mutations in several additional genes are assuming increasing importance. Mutational analysis of certain genes, such as SF3B1, is also becoming an important tool to distinguish subsets of MDS that have different biologic behaviors. It is still uncertain how to optimally combine karyotype with mutation data in diagnosis and risk-stratification of AML and MDS, particularly in cases with multiple mutations and/or several mutationally distinct subclones. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Treacher Collins Syndrome: the genetics of a craniofacial disease.

    Science.gov (United States)

    Kadakia, Sameep; Helman, Samuel N; Badhey, Arvind K; Saman, Masoud; Ducic, Yadranko

    2014-06-01

    The molecular underpinnings of Treacher Collins Syndrome (TCS) are diverse. This article codifies the most recent findings in this complex area of research to further current understanding of the disease process. Elucidating the genetic causes of the disorder can be useful in earlier detection and better treatment planning. Articles from 1991 to 2013 were selected and reviewed by five researchers utilizing the most recent literature of the genetics and pathophysiology of TCS. Mutations in TCOF1, POLR1C and POLR1D have all been implicated in causing TCS. The association of the TCOF1 gene product, Treacle, and gene products of POLR1C and POLR1D with ribosome biosynthesis suggests that a loss of function mutation in these genes disrupts ribosome biosynthesis in constituent neural crest cells and neuroepithelium leading to apoptosis. However, recent data illustrating that P53 heterozygosity is protective against TCS, and that P53 and TCOF1 hemizygous embryos do not affect ribosomal function, implicates P53 or elements downstream of P53 as playing a role in TCS pathogenesis. Our study codified nascent findings of the molecular determinants of TCS. These findings add to a burgeoning database of TCS-associated mutations, and as such, can be used to establish TCS diagnosis and further clarify TCS pathogenesis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Teaching molecular genetics: Chapter 1--Background principles and methods of molecular biology.

    NARCIS (Netherlands)

    Knoers, N.V.A.M.; Monnens, L.A.H.

    2006-01-01

    In this first chapter of the series "Teaching molecular genetics," an introduction to molecular genetics is presented. We describe the structure of DNA and genes and explain in detail the central dogma of molecular biology, that is, the flow of genetic information from DNA via RNA to polypeptide

  1. Plant Genetics and Molecular Biology: An Introduction.

    Science.gov (United States)

    Varshney, Rajeev K; Pandey, Manish K; Chitikineni, Annapurna

    2018-02-16

    The rapidly evolving technologies can serve as a potential growth engine in agriculture as many of these technologies have revolutionized several industries in the recent past. The tremendous advancements in biotechnology methods, cost-effective sequencing technology, refinement of genomic tools, and standardization of modern genomics-assisted breeding methods hold great promise in taking the global agriculture to the next level through development of improved climate-smart seeds. These technologies can dramatically increase our capacity to understand the molecular basis of traits and utilize the available resources for accelerated development of stable high-yielding, nutritious, input-use efficient, and climate-smart crop varieties. This book aimed to document the monumental advances witnessed during the last decade in multiple fields of plant biotechnology such as genetics, structural and functional genomics, trait and gene discovery, transcriptomics, proteomics, metabolomics, epigenomics, nanotechnology, and analytical tools. This book will serve to update the scientific community, academicians, and other stakeholders in global agriculture on the rapid progress in various areas of agricultural biotechnology. This chapter provides a summary of the book, "Plant Genetics and Molecular Biology." Graphical Abstract.

  2. Genetics Home Reference: Li-Fraumeni syndrome

    Science.gov (United States)

    ... syndrome . More than half of all families with Li-Fraumeni syndrome have inherited mutations in the TP53 gene. TP53 is a tumor suppressor gene, which ... the genes associated with Li-Fraumeni syndrome CHEK2 TP53 Related ... syndrome is inherited in an autosomal dominant pattern , which means one ...

  3. Treacher Collins Syndrome; Anesthetic considerations and Molecular Findings

    Directory of Open Access Journals (Sweden)

    Shahram Sayyadi

    2018-01-01

    Full Text Available Treacher Collins Syndrome (TCS is a rare disease with mandibulofacial dysostosis. The deformities accompanied by this syndrome could cause especial challenges for anesthesiologist. On the other hand Treacher protein is well recognized in the pathogenesis of this syndrome. In this report we want to present a successful management of a patient with Treacher Collins syndrome and also describe new advances in the molecular aspect of this disease.

  4. Molecular and genetic basis of X-linked immunodeficiency disorders

    Energy Technology Data Exchange (ETDEWEB)

    Puck, J.M. (National Center for Human Genome Research, Bethesda, MD (United States))

    1994-03-01

    Within a short time interval the specific gene defects causing three X-linked human immunodeficiencies, agammaglobulinemia (XLA), hyper-IgM syndrome (HIGM), and severe combined immunodeficiency (XSCID), have been identified. These represent the first human disease phenotypes associated with each of three gene families already recognized to be important in lymphocyte development and signaling: XLA is caused by mutations of a B cell-specific intracellular tyrosine kinase; HIGM, by mutations in the TNF-related CD40 ligand, through which T cells deliver helper signals by direct contact with B cell CD40; and XSCID, by mutations in the [gamma] chain of the lymphocyte receptor for IL-2. Each patient mutation analyzed to date has been unique, representing both a challenge for genetic diagnosis and management and an important resource for dissecting molecular domains and understanding the physiologic function of the gene products.

  5. [Basal cell carcinoma. Molecular genetics and unusual clinical features].

    Science.gov (United States)

    Reifenberger, J

    2007-05-01

    Basal cell carcinoma is the most common human cancer. Its incidence is steadily increasing. The development of basal cell carcinoma is linked to genetic factors, including the individual skin phototype, as well as the cumulative exposure to UVB. The vast majority of basal cell carcinomas are sporadic tumors, while familial cases associated with certain hereditary syndromes are less common. At the molecular level, basal cell carcinomas are characterized by aberrant activation of sonic hedgehog signaling, usually due to mutations either in the ptch or smoh genes. In addition, about half of the cases carry mutations in the tp53 tumor suppressor gene, which are often UVB-associated C-->T transition mutations. Clinically, basal cell carcinomas may show a high degree of phenotypical variability. In particular, tumors occurring in atypical locations, showing an unusual clinical appearance, or imitating other skin diseases may cause diagnostic problems. This review article summarizes the current state of the art concerning the etiology, predisposition and molecular genetics of basal cell carcinoma. In addition, examples of unusual clinical manifestations are illustrated.

  6. UPDATED MOLECULAR GENETICS AND PATHOGENESIS OF ICHTHYOSES

    Science.gov (United States)

    AKIYAMA, MASASHI

    2011-01-01

    ABSTRACT Research into the molecular genetics and pathomechanisms of ichthyoses have advanced considerably, resulting in the identification of several causative genes and molecules underlying the disease. In 2009, the First Ichthyosis Consensus Conference was held to establish a consensus for the nomenclature and classification of inherited ichthyoses, by which an international consensus for the classification of inherited ichthyosis was achieved. In this review, the pathogeneses of various ichthyoses are summarized based on their revised classification and terminology. Skin barrier defects are involved in the pathogenesis of various types of ichthyosis. The known causative molecules underlying ichthyosis include ABCA12, lipoxygenase-3, 12R-lipoxygenase, CYP4F22, ichthyin and steroid sulfatase, all of which are thought to be related to the intercellular lipid layers. ABCA12 is a known keratinocyte lipid transporter associated with lipid transport in lamellar granules and a loss of ABCA12 function leads to defective lipid transport in the keratinocytes, resulting in the most severe, harlequin ichthyosis phenotype. Other causative molecules for ichthyoses are transglutaminase 1, keratins and filaggrin. Transglutaminase 1 plays a role in cornified cell envelope formation. Keratins 1, 10 and 2 are involved in the keratin network of suprabasal keratinocytes and filaggrin is essential for the formation of keratohyalin granules. It is important to obtain information concerning genetic defects and to elucidate ichthyotic disease pathomechanisms for the establishment of an effective therapy and beneficial genetic counseling, including a prenatal diagnosis for families affected by ichthyotic disease. PMID:21928690

  7. Angelman Syndrome: Genetic Mechanisms and Relationship to Prader-Willi Syndrome.

    Science.gov (United States)

    Smith, Arabella

    1994-01-01

    Research points to two distinct regions within the Prader-Willi chromosome region: one for Prader Willi syndrome and one for Angelman syndrome. Genetic mechanisms in Angelman syndrome are complex, and at present, three mechanisms are recognized: maternal deletion, paternal uniparental disomy, and a nondeleted nondisomic form. (Author/JDD)

  8. Cytogenetic and Molecular Investigation in Children with Possible Fragile X Syndrome

    Directory of Open Access Journals (Sweden)

    Onur Ozer

    2012-04-01

    Full Text Available Objective: Fragile X syndrome (FXS is the most common cause of inherited mental retardation and is due to a mutation in the X-linked FMR1 gene. Molecular genetic testing and chromosome analysis are indicated for this disorder. In this context, we tried to determine the frequency of the FXS, and other chro¬mosomal abnormalities of Turkish pediatric neurology outpatients. Materials and Methods: Cytogenetic and molecular screenings were performed to esti-mate the prevalence of the fragile X in 107 patients with mental retardation, language disorders, hyperactivity, develop¬mental delay or fragile X syndrome phenotype. Only 26 out of 107 patients were screened, molecularly. Results: Cytogenetically fragile X-positive cells was found in 8 cases (7.5% of 107 patients; in 4.7% of males and in 2.8% of females. The autosomal fragile sites (FS was found in 14 (13.1% cases. One (0.9% patient had pericentric inversion of chromosome 9. Molecular analysis were performed for 26 patients and all patients showed normal CGG expansion. Conclusion: In diagnosis of fragile X syndrome, chromosome analysis must be run in conjunction with the molecular studies. It is recommended that all members of the fragile X family under risk should be screened both by cytogenetic and molecular methods. Genetic counseling can be useful to patients and families considering genetic testing. [Cukurova Med J 2012; 37(2.000: 76-83

  9. Genetic anticipation in Swedish Lynch syndrome families.

    Directory of Open Access Journals (Sweden)

    Jenny von Salomé

    2017-10-01

    Full Text Available Among hereditary colorectal cancer predisposing syndromes, Lynch syndrome (LS caused by mutations in DNA mismatch repair genes MLH1, MSH2, MSH6 or PMS2 is the most common. Patients with LS have an increased risk of early onset colon and endometrial cancer, but also other tumors that generally have an earlier onset compared to the general population. However, age at first primary cancer varies within families and genetic anticipation, i.e. decreasing age at onset in successive generations, has been suggested in LS. Anticipation is a well-known phenomenon in e.g neurodegenerative diseases and several reports have studied anticipation in heritable cancer. The purpose of this study is to determine whether anticipation can be shown in a nationwide cohort of Swedish LS families referred to the regional departments of clinical genetics in Lund, Stockholm, Linköping, Uppsala and Umeå between the years 1990-2013. We analyzed a homogenous group of mutation carriers, utilizing information from both affected and non-affected family members. In total, 239 families with a mismatch repair gene mutation (96 MLH1 families, 90 MSH2 families including one family with an EPCAM-MSH2 deletion, 39 MSH6 families, 12 PMS2 families, and 2 MLH1+PMS2 families comprising 1028 at-risk carriers were identified among the Swedish LS families, of which 1003 mutation carriers had available follow-up information and could be included in the study. Using a normal random effects model (NREM we estimate a 2.1 year decrease in age of diagnosis per generation. An alternative analysis using a mixed-effects Cox proportional hazards model (COX-R estimates a hazard ratio of exp(0.171, or about 1.19, for age of diagnosis between consecutive generations. LS-associated gene-specific anticipation effects are evident for MSH2 (2.6 years/generation for NREM and hazard ratio of 1.33 for COX-R and PMS2 (7.3 years/generation and hazard ratio of 1.86. The estimated anticipation effects for MLH1

  10. Angelman-Like Syndrome: A Genetic Approach to Diagnosis with Illustrative Cases

    Directory of Open Access Journals (Sweden)

    Ho-Ming Luk

    2016-01-01

    Full Text Available Epigenetic abnormalities in 15q11-13 imprinted region and UBE3A mutation are the two major mechanisms for molecularly confirmed Angelman Syndrome. However, there is 10% of clinically diagnosed Angelman Syndrome remaining test negative. With the advancement of genomic technology like array comparative genomic hybridization and next generation sequencing methods, it is found that some patients of these test negative Angelman-like Syndromes actually have alternative diagnoses. Accurate molecular diagnosis is paramount for genetic counseling and subsequent management. Despite overlapping phenotypes between Angelman and Angelman-like Syndrome, there are some subtle but distinct features which could differentiate them clinically. It would provide important clue during the diagnostic process for clinicians.

  11. Angelman-Like Syndrome: A Genetic Approach to Diagnosis with Illustrative Cases.

    Science.gov (United States)

    Luk, Ho-Ming

    2016-01-01

    Epigenetic abnormalities in 15q11-13 imprinted region and UBE3A mutation are the two major mechanisms for molecularly confirmed Angelman Syndrome. However, there is 10% of clinically diagnosed Angelman Syndrome remaining test negative. With the advancement of genomic technology like array comparative genomic hybridization and next generation sequencing methods, it is found that some patients of these test negative Angelman-like Syndromes actually have alternative diagnoses. Accurate molecular diagnosis is paramount for genetic counseling and subsequent management. Despite overlapping phenotypes between Angelman and Angelman-like Syndrome, there are some subtle but distinct features which could differentiate them clinically. It would provide important clue during the diagnostic process for clinicians.

  12. Genetics Home Reference: 3q29 microduplication syndrome

    Science.gov (United States)

    ... abnormalities, heart defects, and an unusually small head ( microcephaly ) can occur. 3q29 microduplication syndrome may increase the ... named? Additional Information & Resources MedlinePlus (3 links) Encyclopedia: Microcephaly Encyclopedia: Obesity Health Topic: Developmental Disabilities Genetic and ...

  13. Genetics Home Reference: bare lymphocyte syndrome type II

    Science.gov (United States)

    ... Immunodeficiency Disorders Health Topic: Immune System and Disorders Genetic and Rare Diseases Information Center (1 link) Bare lymphocyte syndrome 2 Additional NIH Resources (1 link) National Institute of Allergy and Infectious Diseases: Primary Immune Deficiency Diseases Educational Resources (6 ...

  14. Nance-Horan syndrome: a contiguous gene syndrome involving deletion of the amelogenin gene? A case report and molecular analysis.

    Science.gov (United States)

    Franco, E; Hodgson, S; Lench, N; Roberts, G J

    1995-03-01

    A case of Nance-Horan syndrome in a male is presented, with some features of the condition in his carrier mother and her mother. It is proposed that Nance-Horan syndrome might be a contiguous gene syndrome mapping to chromosome Xp21.2-p22.3. The proband had congenital cataract microphthalmia and dental abnormalities including screwdriver shaped incisors and evidence of enamel pitting hypoplasia. The region Xp21.2-p22.3 also contains the tooth enamel protein gene, amelogenin (AMGX). Using molecular genetic techniques, we have shown that there is no evidence that the AMGX gene is deleted in this case of the Nance-Horan syndrome.

  15. Morphological and molecular genetic diversity of Syrian indigenous ...

    African Journals Online (AJOL)

    Morphological and molecular genetic diversity of Syrian indigenous goat populations. Halima Hassen, Barbara Rischkowsky, Adnan Termanini, Ghassen Jessry, Aynalem Haile, Michael Baum, Samir Lababidi ...

  16. Molecular research on the genetic diversity of Tunisian date palm ...

    African Journals Online (AJOL)

    Molecular research on the genetic diversity of Tunisian date palm ( Phoenix dactylifera L.) using the random amplified microsatellite polymorphism (RAMPO) and amplified fragment length polymorphism (AFLP) methods.

  17. Molecular Genetic Studies of Some Eye Diseases Affecting the ...

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Molecular Genetic Studies of Some Eye Diseases Affecting the Indian Population. Single gene disorders. Complex eye diseases. Genotype-phenotype correlation. Molecular diagnostics.

  18. Illustration of genetic syndromes in the nursery.

    Science.gov (United States)

    Macnab, A J; Langlois, S

    2006-01-15

    Reading to children and storytelling has documented developmental benefits. Traditional Nursery Rhymes (Mother Goose tales in North America) encapsulate 'snapshots' of the people described and chronicle their customs, superstitions, and amusements. Art has long been employed to document the impact of human imperfections and diseases. We investigated whether illustrations accompanying nursery rhymes, suggest that any characters illustrated may have had or been based on recognized morphological abnormalities, and if this literature documents a role for grandmothers as storytellers. Archival materials were reviewed at the Victoria and Albert museum and Mary Evans picture library, and via the web. As early as 1695, Perrault included a frontispiece of a mature woman as storyteller in his book of fairytales. Similar scenes by various artists (Boilly, Cruikshank, Guy, Highmore, Maclise, Richter, and Smith) are found consistently from 1744 to 1908. Many illustrators (Aldin, Caldecott, Cruikshank, Doré, Dulac, Gale, Greenaway, Rackham, Tarrant, and Wood) portray infants, children, and adults who are dwarfed, giant, or whimsically grotesque. Many images certainly suggest genetic syndromes, and in some characters consistency of specific features is evident between artists. Our research confirms the wealth of children's nursery rhyme illustrations suggesting pathology; that an authoritative compilation of the morphologies depicted is lacking; and that historically, grandmothers have a central role as storytellers. (c) 2005 Wiley-Liss, Inc.

  19. Genetic, chromosomal, and syndromic causes of neural tube defects

    Science.gov (United States)

    Seidahmed, Mohammed Z.; Abdelbasit, Omer B.; Shaheed, Meeralebbae M.; Alhussein, Khalid A.; Miqdad, Abeer M.; Samadi, Abdulmohsen S.; Khalil, Mohammed I.; Al-Mardawi, Elham; Salih, Mustafa A.

    2014-01-01

    Objective: To ascertain the incidence, and describe the various forms of neural tube defects (NTDs) due to genetic, chromosomal, and syndromic causes. Methods: We carried out a retrospective analysis of data retrieved from the medical records of newborn infants admitted to the Neonatal Intensive Care Unit with NTDs and their mothers spanning 14 years (1996-2009) at the Security Forces Hospital, Riyadh, Saudi Arabia. The cases were ascertained by a perinatologist, neonatologist, geneticist, radiologist, and neurologist. The literature was reviewed via a MEDLINE search. Only liveborn babies were included. Permission from the Educational Committee at the Security Forces Hospital was obtained prior to the collection of data. Results: Out of 103 infants with NTDs admitted during this period, 20 (19.4%) were found to have an underlying genetic syndromic, chromosomal and/or other anomalies. There were 5 cases of Meckel-Gruber syndrome, 2 Joubert syndrome, one Waardenburg syndrome, one Walker-Warburg syndrome, 2 chromosomal disorders, 2 caudal regression, one amniotic band disruption sequence, one associated with omphalocele, one with diaphragmatic hernia, and 4 with multiple congenital anomalies. Conclusions: There is a high rate of underlying genetic syndromic and/or chromosomal causes of NTDs in the Saudi Arabian population due to the high consanguinity rate. Identification of such association can lead to more accurate provisions of genetic counseling to the family including preimplantation genetic diagnosis or early termination of pregnancies associated with lethal conditions. PMID:25551112

  20. Chondrosarcoma: With Updates on Molecular Genetics

    Directory of Open Access Journals (Sweden)

    Mi-Jung Kim

    2011-01-01

    Full Text Available Chondrosarcoma (CHS is a malignant cartilage-forming tumor and usually occurs within the medullary canal of long bones and pelvic bones. Based on the morphologic feature alone, a correct diangosis of CHS may be difficult, Therefore, correlation of radiological and clinicopathological features is mandatory in the diagnosis of CHS. The prognosis of CHS is closely related to histologic grading, however, histologic grading may be subjective with high inter-observer variability. In this paper, we present histologic grading system and clinicopathological and radiological findings of conventional CHS. Subtypes of CHSs, such as dedifferentiated, mesenchymal, and clear cell CHSs are also presented. In addition, we introduce updated cytogenetic and molecular genetic findings to expand our understanding of CHS biology. New markers of cell differentiation, proliferation, and cell signaling might offer important therapeutic and prognostic information in near future.

  1. Genetics Home Reference: 3MC syndrome

    Science.gov (United States)

    ... effects of mutations associated with 3MC syndrome. BMC Biol. 2015 Apr 17;13:27. doi: 10.1186/ ... Carnevale, Mingarelli, Malpuech, and Michels (3MC) syndrome. J Biol Chem. 2013 Aug 2;288(31):22399-407. ...

  2. Genetics Home Reference: Bohring-Opitz syndrome

    Science.gov (United States)

    ... Hopkins Medicine: Failure to Thrive KidsHealth from Nemours: Failure to Thrive MalaCards: bohring-opitz syndrome Oregon Health Sciences University: Metopic Synostosis Orphanet: Bohring-Opitz syndrome Patient Support ...

  3. Genetics Home Reference: Lennox-Gastaut syndrome

    Science.gov (United States)

    ... a history of recurrent seizures beginning in infancy (infantile spasms) or a related condition called West syndrome. In ... death among children with Lennox-Gastaut syndrome and infantile spasms. J Child Neurol. 2010 Apr;25(4):441- ...

  4. Genetics Home Reference: Romano-Ward syndrome

    Science.gov (United States)

    ... syndrome, the part of the heartbeat known as the QT interval is abnormally long. Abnormalities in the time it takes to recharge the heart lead ... Clinic Disease InfoSearch: Romano-Ward syndrome KidsHealth from the Nemours ... Consumer Version: Long QT Syndrome My46 Trait Profile Orphanet: Familial ...

  5. Teaching molecular genetics: Chapter 1--Background principles and methods of molecular biology.

    Science.gov (United States)

    Knoers, Nine V A M; Monnens, Leo A H

    2006-02-01

    In this first chapter of the series "Teaching molecular genetics," an introduction to molecular genetics is presented. We describe the structure of DNA and genes and explain in detail the central dogma of molecular biology, that is, the flow of genetic information from DNA via RNA to polypeptide (protein). In addition, several basic and frequently used general molecular tools, such as restriction enzymes, Southern blotting, DNA amplification and sequencing are discussed, in order to lay the foundations for the forthcoming chapters.

  6. Molecular Genetics of Supernumerary Tooth Formation

    Science.gov (United States)

    Wang, Xiu-Ping; Fan, Jiabing

    2011-01-01

    Summary Despite advances in the knowledge of tooth morphogenesis and differentiation, relatively little is known about the aetiology and molecular mechanisms underlying supernumerary tooth formation. A small number of supernumerary teeth may be a common developmental dental anomaly, while multiple supernumerary teeth usually have a genetic component and they are sometimes thought to represent a partial third dentition in humans. Mice, which are commonly used for studying tooth development, only exhibit one dentition, with very few mouse models exhibiting supernumerary teeth similar to those in humans. Inactivation of Apc or forced activation of Wnt/β(catenin signalling results in multiple supernumerary tooth formation in both humans and in mice, but the key genes in these pathways are not very clear. Analysis of other model systems with continuous tooth replacement or secondary tooth formation, such as fish, snake, lizard, and ferret, is providing insights into the molecular and cellular mechanisms underlying succesional tooth development, and will assist in the studies on supernumerary tooth formation in humans. This information, together with the advances in stem cell biology and tissue engineering, will pave ways for the tooth regeneration and tooth bioengineering. PMID:21309064

  7. Genetics Home Reference: 47,XYY syndrome

    Science.gov (United States)

    ... These problems include attention deficit hyperactivity disorder (ADHD); depression; anxiety; and autism spectrum disorder , ... about a genetic condition can statistics provide? Why are some genetic conditions more common ...

  8. Genetics Home Reference: Klippel-Trenaunay syndrome

    Science.gov (United States)

    ... which a genetic condition can be inherited? More about Inheriting Genetic Conditions ... Capillary Malformation (Port Wine Stain) Cincinnati Children's Hospital Medical Center: Capillary Lymphatic ...

  9. Genetics Home Reference: Jervell and Lange-Nielsen syndrome

    Science.gov (United States)

    ... worldwide. This condition has a higher prevalence in Denmark, Sweden, and Norway, where it affects at least ... I. The Jervell and Lange-Nielsen syndrome: natural history, molecular basis, and clinical outcome. Circulation. 2006 Feb ...

  10. A systematic review of genetic syndromes with obesity.

    Science.gov (United States)

    Kaur, Y; de Souza, R J; Gibson, W T; Meyre, D

    2017-06-01

    Syndromic monogenic obesity typically follows Mendelian patterns of inheritance and involves the co-presentation of other characteristics, such as mental retardation, dysmorphic features and organ-specific abnormalities. Previous reviews on obesity have reported 20 to 30 syndromes but no systematic review has yet been conducted on syndromic obesity. We searched seven databases using terms such as 'obesity', 'syndrome' and 'gene' to conduct a systematic review of literature on syndromic obesity. Our literature search identified 13,719 references. After abstract and full-text review, 119 relevant papers were eligible, and 42 papers were identified through additional searches. Our analysis of these 161 papers found that 79 obesity syndromes have been reported in literature. Of the 79 syndromes, 19 have been fully genetically elucidated, 11 have been partially elucidated, 27 have been mapped to a chromosomal region and for the remaining 22, neither the gene(s) nor the chromosomal location(s) have yet been identified. Interestingly, 54.4% of the syndromes have not been assigned a name, whereas 13.9% have more than one name. We report on organizational inconsistencies (e.g. naming discrepancies and syndrome classification) and provide suggestions for improvements. Overall, this review illustrates the need for increased clinical and genetic research on syndromes with obesity. © 2017 World Obesity Federation.

  11. A Catalog of Genetic Syndromes in Childhood Cancer.

    Science.gov (United States)

    Zimmerman, Rheanne; Schimmenti, Lisa; Spector, Logan

    2015-12-01

    Genetic syndromes and pediatric cancers are rare, so instances of co-occurrence raise the question of whether the two conditions may be etiologically linked. Clear examples of causal association can be found in the cancer predisposition syndromes. This report contains the results of a systematic literature search using Ovid Medline for co-occurrence of genetic syndromes with 23 types of pediatric cancer. The results reflect known associations as well as many reports of infrequently observed co-occurrences. This compilation may suggest previously overlooked patterns, and the information could be used to identify gene pathways critical in the development of childhood cancers. © 2015 Wiley Periodicals, Inc.

  12. Long QT syndrome: from genetic basis to treatment

    Directory of Open Access Journals (Sweden)

    Lia Crotti

    2011-11-01

    Full Text Available The congenital long QT syndrome (LQTS is a monogenic disorder, not as rare as it was originally estimated to be, mainly caused by mutations in genes encoding for ion channels. Molecular screening in this disease is part of the diagnostic process and this has already been recognized by current guidelines since 2006. However, very recently, two consensus documents have been published, with the recommendations for the use of genetic testing in the clinical evaluation of genetically transmitted arrhythmogenic diseases. Therefore, we devoted a specific section of the present review to the discussion of these two documents in relation to LQTS. The clinical presentation of the disease is typically characterized by a prolongation of the QT interval on the electrocardiogram (ECG and by the occurrence of syncope or cardiac arrest, mainly precipitated by sympathetic activation. While the diagnosis of typical cases it is quite easy, borderline cases can be quite challenging and therefore the availability of diagnostic criteria is very useful to support the diagnostic process. Very recently, the LQTS diagnostic criteria have been updated and they are presented in the current review. Finally, the clinical management of LQTS patients is presented together with a schematic flow-chart and recent data coming from the LQTS-ICD European registry are illustrated. The last part of the review is dedicated at future perspectives and latest results on modifier genes and stem cells are presented.

  13. Genetic Counseling and Mongolism (Down's Syndrome): Prediction, Detection, Prevention.

    Science.gov (United States)

    Schlichte, John E.

    Intended for use by the public as well as by medical professionals and related service agencies, the booklet presents genetic counseling as a means of providing information to deal with genetic disorders in general and mongolism (Down's syndrome) in particular. Characteristics of mongolism and possible emotional effects on the family of a…

  14. Genetics Home Reference: Sjögren syndrome

    Science.gov (United States)

    ... syndrome in particular. The inheritance pattern of this predisposition is unknown. Related Information What does it mean if a disorder seems to run in my family? What are the different ways in which a genetic condition can be inherited? More about Inheriting Genetic ...

  15. Molecular genetics and cytogenetics of myeloproliferative disorders.

    Science.gov (United States)

    Bench, A J; Nacheva, E P; Champion, K M; Green, A R

    1998-12-01

    The myeloproliferative disorders are believed to represent clonal malignancies resulting from transformation of a pluripotent stem cell. X-inactivation patterns of peripheral blood cells have been proposed as a useful diagnostic tool but this method is limited by the finding of a clonal X-inactivation pattern in a significant proportion of normal elderly women. There is no pathognomonic chromosomal abnormality associated with the myeloproliferative disorders. However, consistent acquired cytogenetic changes include del(20q), del(13q), trisomy 8 and 9 and duplication of segments of 1q, all of which have been observed at diagnosis or before cytoreductive therapy and therefore represent early lesions which contribute to the pathogenesis of these disorders. Although, the acquired molecular defects underlying most myeloproliferative disorders have not yet been elucidated, translocations associated with the rare 8p11 syndrome have permitted identification of a novel fusion protein. The role of a number of candidate genes in the other myeloproliferative disorders has also been studied, but no mutations have been identified so far. It is likely that a number of genes will be involved, given the varied phenotypes of the diseases. Identification of causal genes will be of considerable interest to both clinicians, who currently lack a specific and sensitive diagnostic test, and scientists interested in fundamental issues of stem cell behaviour.

  16. [Turner syndrome and genetic polymorphism: a systematic review].

    Science.gov (United States)

    Trovó de Marqui, Alessandra Bernadete

    2015-01-01

    To present the main results of the literature on genetic polymorphisms in Turner Syndrome and their association with the clinical signs and the etiology of this chromosomal disorder. The review was conducted in the PubMed database without any time limit, using the terms Turner syndrome and genetic polymorphism. A total of 116 articles were found, and based on the established inclusion and exclusion criteria 17 were selected for the review. The polymorphisms investigated in patients with Turner Syndrome were associated with growth deficit, causing short stature, low bone mineral density, autoimmunity and cardiac abnormalities, which are frequently found in patients with Turner Syndrome. The role of single nucleotide polymorphisms (SNPs) in the etiology of Turner syndrome, i.e., in chromosomal nondisjunction, was also confirmed. Genetic polymorphisms appear to be associated with Turner Syndrome. However, in view of the small number of published studies and their contradictory findings, further studies in different populations are needed in order to clarify the role of genetic variants in the clinical signs and etiology of the Turner Syndrome. Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  17. Neurophysiology versus clinical genetics in Rett syndrome: A multicenter study

    Science.gov (United States)

    Halbach, Nicky; Julu, Peter; Witt‐Engerström, Ingegerd; Pini, Giorgio; Bigoni, Stefania; Hansen, Stig; Apartopoulos, Flora; Delamont, Robert; van Roozendaal, Kees; Scusa, Maria F.; Borelli, Paolo; Candel, Math; Curfs, Leopold

    2016-01-01

    Many studies have attempted to establish the genotype–phenotype correlation in Rett syndrome (RTT). Cardiorespiratory measurements provide robust objective data, to correlate with each of the different clinical phenotypes. It has important implications for the management and treatment of this syndrome. The aim of this study was to correlate the genotype with the quantitative cardiorespiratory data obtained by neurophysiological measurement combined with a clinical severity score. This international multicenter study was conducted in four European countries from 1999 to 2012. The study cohort consisted of a group of 132 well‐defined RTT females aged between 2 and 43 years with extended clinical, molecular, and neurophysiological assessments. Diagnosis of RTT was based on the consensus criteria for RTT and molecular confirmation. Genotype–phenotype analyses of clinical features and cardiorespiratory data were performed after grouping mutations by the same type and localization or having the same putative biological effect on the MeCP2 protein, and subsequently on eight single recurrent mutations. A less severe phenotype was seen in females with CTS, p.R133C, and p.R294X mutations. Autonomic disturbances were present in all females, and not restricted to nor influenced by one specific group or any single recurrent mutation. The objective information from non‐invasive neurophysiological evaluation of the disturbed central autonomic control is of great importance in helping to organize the lifelong care for females with RTT. Further research is needed to provide insights into the pathogenesis of autonomic dysfunction, and to develop evidence‐based management in RTT. © 2016 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals, Inc. PMID:27354166

  18. Characterizing genetic syndromes involved in cancer and radiogenic cancer risk

    International Nuclear Information System (INIS)

    Unrau, P.; Doerffer, K.

    1998-01-01

    The COG project 2806A (1995), reviewed the On-line Mendelian Inheritance in Man (OMIM) database of genetic syndromes to identify those syndromes, genes, and DNA sequences implicated in some way in the cancer process, and especially in radiogenic cancer risk. The current report describes a recent update of the survey in light of two years of further progress in the Human Genome project, and is intended to supply a comprehensive list of those genetic syndromes, genes, DNA sequences and map locations that define genes likely to be involved in cancer risk. Of the 8203 syndromes in OMIM in 1997 June, 814 are associated, even if marginally, with cancer. Of the 814 syndromes so linked, 672 have been mapped to a chromosome, and 476 have been mapped to a chromosome and had a DNA sequence associated with their messenger RNA (or cDNA) sequences. In addition, 35 syndromes have sequences not associated with map locations, and the remaining 107 have neither been mapped nor sequenced. We supply the list of the various genetic syndromes sorted by chromosome location and by OMIM descriptor, together with all the associated but unmapped and unsequenced syndromes. (author)

  19. Practice guidelines for the molecular analysis of Prader-Willi and Angelman syndromes

    Directory of Open Access Journals (Sweden)

    Birch Rachael

    2010-05-01

    Full Text Available Abstract Background Prader-Willi syndrome (PWS and Angelman syndrome (AS are clinically distinct neurodevelopmental genetic disorders that map to 15q11-q13. The primary phenotypes are attributable to loss of expression of imprinted genes within this region which can arise by means of a number of mechanisms. The most sensitive single approach to diagnosing both PWS and AS is to study methylation patterns within 15q11-q13; however many techniques exist for this purpose. Given the diversity of techniques available, there is a need for consensus testing and reporting guidelines. Methods Testing and reporting guidelines have been drawn up and agreed in accordance with the procedures of the UK Clinical Molecular Genetics Society and the European Molecular Genetics Quality Network. Results A practical set of molecular genetic testing and reporting guidelines has been developed for these two disorders. In addition, advice is given on appropriate reporting policies, including advice on test sensitivity and recurrence risks. In considering test sensitivity, the possibility of differential diagnoses is discussed. Conclusion An agreed set of practice guidelines has been developed for the diagnostic molecular genetic testing of PWS and AS.

  20. Duplication 3q syndrome: Molecular delineation of the critical region

    Energy Technology Data Exchange (ETDEWEB)

    Aqua, M.S.; Rizzu, P.; Lindsay, E.A. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1995-01-02

    The phenotype of dup(3q) syndrome partially overlaps with Brachmann-de Lange phenotype. Convulsions and eye, palate renal, and cardiac anomalies are more frequent in dup(3q) syndrome, while limb deficiencies, hirsutism, and synophrys are more characteristic of Brachmann-de Lange syndrome. Whether the two syndromes have a biological relationship has yet to be demonstrated. Using two patient translocation cell lines, each involving distal 3q, we have narrowed the critical region of the dup(3q) syndrome to the interval 3q26.31-q27.3 and initiated its molecular characterization. We have mapped in this region 6 cosmid clones spanning approximately 3 - 5 Mb. The critical region appears to overlap with the region where a balanced translocation was found in a Brachmann-de Lange patient. This work provides the mapping framework for finer molecular analysis dup(3q) syndrome. 25 refs., 3 figs.

  1. Cystic fibrosis, molecular genetics for all life

    Directory of Open Access Journals (Sweden)

    Ausilia Elce

    2015-10-01

    Full Text Available Cystic fibrosis (CF is the most frequent lethal autosomal recessive disorder among Caucasians (incidence: 1:2,500 newborn. In the last two decades CF prognosis considerably improved and many patients well survive into their adulthood. Furthermore, milder CF with a late onset was described. CF is a challenge for laboratory of molecular genetics that greatly contributes to the natural history of the disease since fetal age. Carrier screening and prenatal diagnosis, also by non-invasive analysis of maternal blood fetal DNA, are now available, and many labs offer preimplantation diagnosis. The major criticism in prenatal medicine is the lack of an effective multidisciplinary counseling that helps the couples to plan their reasoned reproductive choice. Most countries offer newborn screening that significantly reduce CF morbidity but different protocols based on blood trypsin, molecular analysis and sweat chloride cause a variable efficiency of the screening programs. Again, laboratory is crucial for CF diagnosis in symptomatic patients: sweat chloride is the diagnostic golden standard, but different methodologies and the lack of quality control in most labs reduce its effectiveness. Molecular analysis contributes to confirm diagnosis in symptomatic subjects; furthermore, it helps to predict the disease outcome on the basis of the mutation (genotype-phenotype correlation and mutations in a myriad of genes, inherited independently by CF transmembrane conductance regulator (CFTR, which may modulate the clinical expression of the disease in each single patient (modifier genes. More recently, the search of the CFTR mutations gained a role in selecting CF patients that may benefit from biological therapy based on correctors and potentiators that are effective in patients bearing specific mutations (personalized therapy. All such applications of molecular diagnostics confirm the “uniqueness” of each CF patient, offering to laboratory medicine the

  2. Application of molecular genetic tools for forest pathology

    Science.gov (United States)

    Mee-Sook Kim; John Hanna; Amy Ross-Davis; Ned Klopfenstein

    2012-01-01

    In recent years, advances in molecular genetics have provided powerful tools to address critical issues in forest pathology to help promote resilient forests. Although molecular genetic tools are initially applied to understand individual components of forest pathosystems, forest pathosystems involve dynamic interactions among biotic and abiotic components of the...

  3. Child Development and Molecular Genetics: 14 Years Later

    Science.gov (United States)

    Plomin, Robert

    2013-01-01

    Fourteen years ago, the first article on molecular genetics was published in this journal: "Child Development, Molecular Genetics, and What to Do With Genes Once They Are Found" (R. Plomin & M. Rutter, 1998). The goal of the article was to outline what developmentalists can do with genes once they are found. These new directions for developmental…

  4. Hamartomatous polyps - a clinical and molecular genetic study.

    Science.gov (United States)

    Jelsig, Anne Marie

    2016-08-01

    Hamartomatous polyps (HPs) in the gastrointestinal (GI) tract are rare compared to other types of GI polyps, yet they are the most common type of polyp in children. The symptoms are usually rectal bleeding, abdominal pain, obstipation, anaemia, and/or small bowel obstruction. The polyps are typically removed concurrently with endoscopy when located in the colon, rectum, or stomach, whereas polyps in the small bowel are removed during push-enteroscopy, device-assisted enteroscopy, or by surgery. HPs can be classified as juvenile polyps or Peutz-Jeghers polyps based on their histopathological appearance. Patients with one or a few juvenile polyps are usually not offered clinical follow-up as the polyp(s) are considered not to harbour any malignant potential. Nevertheless, it is important to note that juvenile polyps and HPs are also found in patients with hereditary hamartomatous polyposis syndromes (HPS). Patients with HPS have an increased risk of cancer, recurrences of polyps, and extraintestinal complications. The syndromes are important to diagnose, as patients should be offered surveillance from childhood or early adolescence. The syndromes include juvenile polyposis syndrome, Peutz-Jeghers syndrome, and the PTEN hamartoma tumour syndrome. Currently, the HPS diagnoses are based on clinical criteria and are often assisted with genetic testing as candidate genes have been described for each syndrome. This thesis is based on six scientific papers. The overall aim of the studies was to expand the knowledge on clinical course and molecular genetics in patients with HPs and HPS, and to investigate research participants' attitude towards the results of extensive genetic testing.   Paper I: In the first paper we investigated the occurrence, anatomic distribution, and other demographics of juvenile polyps in the colon and rectum in Denmark in 1995-2014. Based on the Danish Pathology Data Bank we found that 1772 patients had 2108 JPs examined in the period, and we

  5. Overview of molecular, cellular, and genetic neurotoxicology.

    Science.gov (United States)

    Wallace, David R

    2005-05-01

    It has become increasingly evident that the field of neurotoxicology is not only rapidly growing but also rapidly evolving, especially over the last 20 years. As the number of drugs and environmental and bacterial/viral agents with potential neurotoxic properties has grown, the need for additional testing has increased. Only recently has the technology advanced to a level that neurotoxicologic studies can be performed without operating in a "black box." Examination of the effects of agents that are suspected of being toxic can occur on the molecular (protein-protein), cellular (biomarkers, neuronal function), and genetic (polymorphisms) level. Together, these areas help to elucidate the potential toxic profiles of unknown (and in some cases, known) agents. The area of proteomics is one of the fastest growing areas in science and particularly applicable to neurotoxicology. Lubec et al, provide a review of the potential and limitations of proteomics. Proteomics focuses on a more comprehensive view of cellular proteins and provides considerably more information about the effects of toxins on the CNS. Proteomics can be classified into three different focuses: post-translational modification, protein-expression profiling, and protein-network mapping. Together, these methods represent a more complete and powerful image of protein modifications following potential toxin exposure. Cellular neurotoxicology involves many cellular processes including alterations in cellular energy homeostasis, ion homeostasis, intracellular signaling function, and neurotransmitter release, uptake, and storage. The greatest hurdle in cellular neurotoxicology has been the discovery of appropriate biomarkers that are reliable, reproducible, and easy to obtain. There are biomarkers of exposure effect, and susceptibility. Finding the appropriate biomarker for a particular toxin is a daunting task. The appropriate biomarker for a particular toxin is a daunting task. The advantage to biomarker

  6. HEREDITARY DISEASES AND SYNDROMES ACCOMPANIED BY FEBRILE CONVULSIONS: CLINICAL AND GENETIC CHARACTERISTICS AND DIAGNOSTIC PROCEDURES

    Directory of Open Access Journals (Sweden)

    E. L. Dadali

    2016-01-01

    Full Text Available The authors provide a review of the clinical and genetic characteristics of hereditary diseases and syndromes accompanied by febrile convulsions, which is illustrated by examples of their own observations. The paper sets forth the possibilities and limitations of using current methods for the molecular genetic diagnosis of idiopathic and symptomatic epilepsies. The most effective and less expensive technique of molecular genetic analysis is shown to be an exome sequencing test using the panels of genes responsible for the occurrence of diseases with simi1ar clinical symptoms. The paper also presents the structure of the panel of genes responsible for the occurrence of monogenic epilepsies, which has been designed at the Genomed Clinic and includes 448 genetic variants. It also determines the significance of using a chromosomal microarray analysis to diagnose both chromosomal and monogenic diseases accompanied by convulsions. 

  7. Genetic Aspects of Preeclampsia and the HELLP Syndrome

    Science.gov (United States)

    Mortensen, Jan Helge; Nagy, Bálint

    2014-01-01

    Both preeclampsia and the HELLP syndrome have their origin in the placenta. The aim of this study is to review genetic factors involved in development of preeclampsia and the HELLP syndrome using literature search in PubMed. A familial cohort links chromosomes 2q, 5q, and 13q to preeclampsia. The chromosome 12q is coupled with the HELLP syndrome. The STOX1 gene, the ERAP1 and 2 genes, the syncytin envelope gene, and the −670 Fas receptor polymorphisms are involved in the development of preeclampsia. The ACVR2A gene on chromosome 2q22 is also implicated. The toll-like receptor-4 (TLR-4) and factor V Leiden mutation participate both in development of preeclampsia and the HELLP syndrome. Carriers of the TT and the CC genotype of the MTHFR C677T polymorphism seem to have an increased risk of the HELLP syndrome. The placental levels of VEGF mRNA are reduced both in women with preeclampsia and in women with the HELLP syndrome. The BclI polymorphism is engaged in development of the HELLP syndrome but not in development of severe preeclampsia. The ACE I/D polymorphism affects uteroplacental and umbilical artery blood flows in women with preeclampsia. In women with preeclampsia and the HELLP syndrome several genes in the placenta are deregulated. Preeclampsia and the HELLP syndrome are multiplex genetic diseases. PMID:24991435

  8. Genetic Aspects of Preeclampsia and the HELLP Syndrome

    Directory of Open Access Journals (Sweden)

    Kjell Haram

    2014-01-01

    Full Text Available Both preeclampsia and the HELLP syndrome have their origin in the placenta. The aim of this study is to review genetic factors involved in development of preeclampsia and the HELLP syndrome using literature search in PubMed. A familial cohort links chromosomes 2q, 5q, and 13q to preeclampsia. The chromosome 12q is coupled with the HELLP syndrome. The STOX1 gene, the ERAP1 and 2 genes, the syncytin envelope gene, and the −670 Fas receptor polymorphisms are involved in the development of preeclampsia. The ACVR2A gene on chromosome 2q22 is also implicated. The toll-like receptor-4 (TLR-4 and factor V Leiden mutation participate both in development of preeclampsia and the HELLP syndrome. Carriers of the TT and the CC genotype of the MTHFR C677T polymorphism seem to have an increased risk of the HELLP syndrome. The placental levels of VEGF mRNA are reduced both in women with preeclampsia and in women with the HELLP syndrome. The BclI polymorphism is engaged in development of the HELLP syndrome but not in development of severe preeclampsia. The ACE I/D polymorphism affects uteroplacental and umbilical artery blood flows in women with preeclampsia. In women with preeclampsia and the HELLP syndrome several genes in the placenta are deregulated. Preeclampsia and the HELLP syndrome are multiplex genetic diseases.

  9. Genetic Causes of Syndromic and Non-Syndromic Autism

    Science.gov (United States)

    Caglayan, Ahmet O.

    2010-01-01

    Aims: Over the past decade, genetic tests have become available for numerous heritable disorders, especially those whose inheritance follows the Mendelian model. Autism spectrum disorders (ASDs) represent a group of developmental disorders with a strong genetic basis. During the past few years, genetic research in ASDs has been successful in…

  10. Circadian rhythms and metabolic syndrome: from experimental genetics to human disease.

    Science.gov (United States)

    Maury, Eleonore; Ramsey, Kathryn Moynihan; Bass, Joseph

    2010-02-19

    The incidence of the metabolic syndrome represents a spectrum of disorders that continue to increase across the industrialized world. Both genetic and environmental factors contribute to metabolic syndrome and recent evidence has emerged to suggest that alterations in circadian systems and sleep participate in the pathogenesis of the disease. In this review, we highlight studies at the intersection of clinical medicine and experimental genetics that pinpoint how perturbations of the internal clock system, and sleep, constitute risk factors for disorders including obesity, diabetes mellitus, cardiovascular disease, thrombosis and even inflammation. An exciting aspect of the field has been the integration of behavioral and physiological approaches, and the emerging insight into both neural and peripheral tissues in disease pathogenesis. Consideration of the cell and molecular links between disorders of circadian rhythms and sleep with metabolic syndrome has begun to open new opportunities for mechanism-based therapeutics.

  11. Repint of "Reframing autism as a behavioral syndrome and not a specific mental disorder: Implications of genetic and phenotypic heterogeneity".

    Science.gov (United States)

    Tordjman, S; Cohen, D; Anderson, G M; Botbol, M; Canitano, R; Coulon, N; Roubertoux, P L

    2018-06-01

    Clinical and molecular genetics have advanced current knowledge on genetic disorders associated with autism. A review of diverse genetic disorders associated with autism is presented and for the first time discussed extensively with regard to possible common underlying mechanisms leading to a similar cognitive-behavioral phenotype of autism. The possible role of interactions between genetic and environmental factors, including epigenetic mechanisms, is in particular examined. Finally, the pertinence of distinguishing non-syndromic autism (isolated autism) from syndromic autism (autism associated with genetic disorders) will be reconsidered. Given the high genetic and etiological heterogeneity of autism, autism can be viewed as a behavioral syndrome related to known genetic disorders (syndromic autism) or currently unknown disorders (apparent non-syndromic autism), rather than a specific categorical mental disorder. It highlights the need to study autism phenotype and developmental trajectory through a multidimensional, non-categorical approach with multivariate analyses within autism spectrum disorder but also across mental disorders, and to conduct systematically clinical genetic examination searching for genetic disorders in all individuals (children but also adults) with autism. Copyright © 2018. Published by Elsevier Ltd.

  12. Reframing autism as a behavioral syndrome and not a specific mental disorder: Implications of genetic and phenotypic heterogeneity.

    Science.gov (United States)

    Tordjman, S; Cohen, D; Coulon, N; Anderson, G M; Botbol, M; Canitano, R; Roubertoux, P L

    2017-01-30

    Clinical and molecular genetics have advanced current knowledge on genetic disorders associated with autism. A review of diverse genetic disorders associated with autism is presented and for the first time discussed extensively with regard to possible common underlying mechanisms leading to a similar cognitive-behavioral phenotype of autism. The possible role of interactions between genetic and environmental factors, including epigenetic mechanisms, is in particular examined. Finally, the pertinence of distinguishing non-syndromic autism (isolated autism) from syndromic autism (autism associated with genetic disorders) will be reconsidered. Given the high genetic and etiological heterogeneity of autism, autism can be viewed as a behavioral syndrome related to known genetic disorders (syndromic autism) or currently unknown disorders (apparent non-syndromic autism), rather than a specific categorical mental disorder. It highlights the need to study autism phenotype and developmental trajectory through a multidimensional, non-categorical approach with multivariate analyses within autism spectrum disorder but also across mental disorders, and to conduct systematically clinical genetic examination searching for genetic disorders in all individuals (children but also adults) with autism. Copyright © 2017. Published by Elsevier Ltd.

  13. Genetics Home Reference: short QT syndrome

    Science.gov (United States)

    ... and can lead to the abnormal heart rhythms characteristic of short QT syndrome . Some affected individuals do not have an identified ... C, Giustetto C, Gaita F, Borggrefe M. Clinical characteristics and treatment of short QT syndrome. Expert Rev Cardiovasc Ther. 2005 Jul;3(4): ...

  14. Genetics Home Reference: Sézary syndrome

    Science.gov (United States)

    ... A, Şanlı H. Transformation of Mycosis fungoides/Sezary syndrome: clinical characteristics and prognosis. Turk J Haematol. 2017 May 23. doi: 10.4274/tjh.2016.0502. [Epub ahead of print] Citation on ... lymphoma (mycosis fungoides and Sezary syndrome). Br J Haematol. 2011 Oct;155(2):150- ...

  15. Genetics Home Reference: Muckle-Wells syndrome

    Science.gov (United States)

    ... syndrome: clinical and histological skin findings compatible with cold air urticaria in a large kindred. Br J Dermatol. 2004 Jul;151(1):99-104. Citation on PubMed Hawkins PN, Lachmann HJ, McDermott MF. Interleukin-1-receptor antagonist in the Muckle-Wells syndrome. N Engl ...

  16. Genetics of the Meckel Syndrome (Dysencephalia Splanchnocystica)

    Science.gov (United States)

    Hsia, Y. E.; And Others

    1971-01-01

    Reported are seven cases in two families of the Meckel syndrome, whose key features are occipital encephalocele, cleft lip and palate, polydactyly, and polycystic kidneys. Evidence supports the hypothesis that the syndrome is a recessively inherited condition, determined by homozygous expression of a single autosomal gene. (Author/KW)

  17. Genetics Home Reference: osteoporosis-pseudoglioma syndrome

    Science.gov (United States)

    ... PubMed Levasseur R, Lacombe D, de Vernejoul MC. LRP5 mutations in osteoporosis-pseudoglioma syndrome and high-bone-mass disorders. Joint ... G, Emi M, Hasegawa T. Various types of LRP5 mutations in four patients with osteoporosis-pseudoglioma syndrome: identification of a 7.2-kb ...

  18. Genetics Home Reference: Potocki-Lupski syndrome

    Science.gov (United States)

    ... cause the disorder. Most cases of Potocki-Lupski syndrome result from a new (de novo) chromosomal duplication and occur in people with ... or Free article on PubMed Central Treadwell-Deering DE, ... of the Potocki-Lupski syndrome (duplication 17p11.2). J Dev Behav Pediatr. 2010 ...

  19. Genetics Home Reference: Loeys-Dietz syndrome

    Science.gov (United States)

    ... Coucke PJ, Cameron DE, Braverman AC, Byers PH, De Paepe AM, Dietz HC. Aneurysm syndromes caused by mutations in the TGF-beta receptor. ... C, Renard M, Loeys B. The Loeys-Dietz syndrome: an update for the clinician. Curr Opin Cardiol. ... on PubMed van de Laar IM, van der Linde D, Oei EH, ...

  20. Genetics Home Reference: Prader-Willi syndrome

    Science.gov (United States)

    ... caused by a phenomenon called genomic imprinting. Most cases of Prader-Willi syndrome (about 70 percent) occur when a segment of ... More about Mutations and Health Inheritance Pattern Most cases of Prader-Willi syndrome are not inherited, particularly those caused by a ...

  1. Genetics Home Reference: Freeman-Sheldon syndrome

    Science.gov (United States)

    ... People with this disorder may have difficulty swallowing (dysphagia), a failure to gain weight and grow at ... Drug Therapy Genetic Counseling Palliative Care Surgery and Rehabilitation Related Information How are genetic conditions diagnosed? How ...

  2. Genetics Home Reference: lateral meningocele syndrome

    Science.gov (United States)

    ... or the genitourinary system, poor feeding, difficulty swallowing (dysphagia), and backflow of stomach acids into the esophagus ( ... Drug Therapy Genetic Counseling Palliative Care Surgery and Rehabilitation Related Information How are genetic conditions diagnosed? How ...

  3. Genetics Home Reference: Woodhouse-Sakati syndrome

    Science.gov (United States)

    ... can include difficulty with speech (dysarthria) or swallowing (dysphagia), mild intellectual disability, and hearing loss caused by ... Drug Therapy Genetic Counseling Palliative Care Surgery and Rehabilitation Related Information How are genetic conditions diagnosed? How ...

  4. DataGenno: building a new tool to bridge molecular and clinical genetics

    Directory of Open Access Journals (Sweden)

    Fabricio F Costa

    2011-03-01

    Full Text Available Fabricio F Costa1,2, Luciano S Foly1, Marcelo P Coutinho11DataGenno Interactive Research Ltd., Itaperuna, Rio de Janeiro, Brazil; 2Cancer Biology and Epigenomics Program, Children's Memorial Research Center, Northwestern University's Feinberg School of Medicine, Chicago, IL, USAAbstract: Clinical genetics is one of the most challenging fields in medicine, with thousands of children born every year with congenital defects that have no satisfactory diagnosis. There are more than 6,000 known single-gene disorders that can cause birth defects or diseases in approximately 1 in every 200 births. Clinical and molecular information on genetic diseases and syndromes are widespread in the literature, and there are few databases combining this information. Therefore, it is very challenging for health care professionals and researchers to translate the latest advances in science and medicine into effective clinical interventions and new treatments. In order to overcome this obstacle and promote networking, we are building DataGenno, an online medical and scientific portal. DataGenno has been developed to be a source of information on genetic diseases and syndromes for the needs of all heath care professionals and researchers. Our database will be able to integrate both clinical and molecular aspects of genetic diseases in a fully interactive environment. DataGenno’s system already contains clinical and molecular information for 300 diseases, with approximately 6,000 signs and symptoms of these diseases in a database combined with a search engine. Our main goal is to cover all genetic diseases described to date, providing not only clinical information such as morphological and anatomical features but also the most comprehensive molecular genetics/genomics features and available testing information. We are also developing ways to connect DataGenno’s portal with Electronic Health Records in order to improve the efficiency of patient care. Additionally

  5. Joubert syndrome: neuroimaging findings in 110 patients in correlation with cognitive function and genetic cause.

    Science.gov (United States)

    Poretti, Andrea; Snow, Joseph; Summers, Angela C; Tekes, Aylin; Huisman, Thierry A G M; Aygun, Nafi; Carson, Kathryn A; Doherty, Dan; Parisi, Melissa A; Toro, Camilo; Yildirimli, Deniz; Vemulapalli, Meghana; Mullikin, Jim C; Cullinane, Andrew R; Vilboux, Thierry; Gahl, William A; Gunay-Aygun, Meral

    2017-08-01

    Joubert syndrome is a clinically and genetically heterogeneous ciliopathy. Neuroimaging findings have not been systematically evaluated in a large cohort of patients with Joubert syndrome in correlation with molecular genetic cause and cognitive function. Brain MRI of 110 patients with Joubert syndrome was included in this study. A comprehensive evaluation of brain MRI studies for infratentorial and supratentorial morphological abnormalities was performed. Genetic cause was identified by whole-exome sequencing, and cognitive functions were assessed with age-appropriate neurocognitive tests in a subset of patients. The cerebellar hemispheres were enlarged in 18% of the patients, mimicking macrocerebellum. The posterior fossa was enlarged in 42% of the patients, resembling Dandy-Walker malformation. Abnormalities of the brainstem, such as protuberance at the ventral contour of the midbrain, were present in 66% of the patients. Abnormalities of the supratentorial brain were present in approximately one-third of the patients, most commonly malrotation of the hippocampi. Mild ventriculomegaly, which typically did not require shunting, was present in 23% of the patients. No correlation between neuroimaging findings and molecular genetic cause was apparent. A novel predictor of outcome was identified; the more severe the degree of vermis hypoplasia, the worse the neurodevelopmental outcome was. The spectrum of neuroimaging findings in Joubert syndrome is wide. Neuroimaging does not predict the genetic cause, but may predict the neurodevelopmental outcome. A high degree of vermis hypoplasia correlates with worse neurodevelopmental outcome. This finding is important for prognostic counselling in Joubert syndrome. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  6. Molecular characterization of a patient presumed to have prader-willi syndrome.

    Science.gov (United States)

    Falaleeva, Marina; Sulsona, Carlos R; Zielke, Horst R; Currey, Kathleen M; de la Grange, Pierre; Aslanzadeh, Vahid; Driscoll, Daniel J; Stamm, Stefan

    2013-01-01

    Prader-Willi syndrome (PWS) is caused by the loss of RNA expression from an imprinted region on chromosome 15 that includes SNRPN, SNORD115, and SNORD116. Currently, there are no mouse models that faithfully reflect the human phenotype and investigations rely on human post-mortem material. During molecular characterization of tissue deposited in a public brain bank from a patient diagnosed with Prader-Willi syndrome, we found RNA expression from SNRPN, SNORD115, and SNORD116 which does not support a genetic diagnosis of Prader-Willi syndrome. The patient was a female, Caucasian nursing home resident with history of morbid obesity (BMI 56.3) and mental retardation. She died at age of 56 from pulmonary embolism. SNORD115 and SNORD116 are unexpectedly stable in post mortem tissue and can be used for post-mortem diagnosis. Molecular characterization of PWS tissue donors can confirm the diagnosis and identify those patients that have been misdiagnosed.

  7. Genetics Home Reference: Donnai-Barrow syndrome

    Science.gov (United States)

    ... tubes in the kidneys where urine is formed ( renal tubules ). LRP2 gene mutations that cause Donnai-Barrow syndrome ... protein. The lack of functional megalin in the renal tubules causes megalin's various ligands to be excreted in ...

  8. Genetics Home Reference: renal coloboma syndrome

    Science.gov (United States)

    ... is unable to aid in development, causing incomplete formation of certain tissues. Why the kidneys and eyes ... 820-6. Citation on PubMed Bower MA, Schimmenti LA, Eccles MR. Renal Coloboma Syndrome. 2007 Jun 8 [ ...

  9. Genetics Home Reference: Brooke-Spiegler syndrome

    Science.gov (United States)

    ... been unclear; while previously thought to derive from sweat glands, they are now generally believed to begin in hair follicles. The tumors associated with Brooke-Spiegler syndrome are generally noncancerous ( ...

  10. Genetics Home Reference: cyclic vomiting syndrome

    Science.gov (United States)

    ... infections. Other triggers can include periods without eating (fasting), temperature extremes, lack of sleep, overexertion, allergies, ingesting ... include changes in brain function, hormonal abnormalities, and gastrointestinal problems. Many researchers believe that cyclic vomiting syndrome ...

  11. Genetics Home Reference: familial cold autoinflammatory syndrome

    Science.gov (United States)

    ... AUTOINFLAMMATORY SYNDROME 2 Sources for This Page Aksentijevich I, D Putnam C, Remmers EF, Mueller JL, Le J, Kolodner RD, Moak Z, Chuang M, Austin F, Goldbach-Mansky R, Hoffman HM, Kastner DL. The ...

  12. Genetics Home Reference: Coffin-Lowry syndrome

    Science.gov (United States)

    ... in cell signaling pathways that are required for learning, the formation of long-term memories, and the ... RC, Tolmie JL, McWilliam RC, Zuberi SM. The movement disorders of Coffin-Lowry syndrome. Brain Dev. 2005 Mar; ...

  13. Genetics Home Reference: Mowat-Wilson syndrome

    Science.gov (United States)

    ... is often associated with an unusually small head ( microcephaly ), structural brain abnormalities, and intellectual disability ranging from ... for This Condition Hirschsprung disease-mental retardation syndrome microcephaly, mental retardation, and distinct facial features, with or ...

  14. Genetics Home Reference: SATB2-associated syndrome

    Science.gov (United States)

    ... from the University of Kansas Medical Center: Facial Anomalies/Craniofacial Conditions SATB2gene.com The Arc: For People with Intellectual and ... Chromosome 2q32-q33 deletion syndrome Sources for This Page ...

  15. Genetics Home Reference: Dubin-Johnson syndrome

    Science.gov (United States)

    ... Jews in Israel. Additionally, several people in the Japanese population have been diagnosed with Dubin-Johnson syndrome . ... of Medicine Lister Hill National Center for Biomedical Communications 8600 Rockville Pike, Bethesda, MD 20894, USA HONCode ...

  16. Genetics Home Reference: Shwachman-Diamond syndrome

    Science.gov (United States)

    ... fatty, foul-smelling stools (steatorrhea); are slow to grow and gain weight (failure to thrive); and experience malnutrition. Pancreatic insufficiency often improves with age in people with Shwachman-Diamond syndrome . Skeletal abnormalities are another common feature of ...

  17. Genetics Home Reference: Bardet-Biedl syndrome

    Science.gov (United States)

    ... poor visual acuity) and become legally blind by adolescence or early adulthood. Obesity is another characteristic feature of Bardet-Biedl syndrome . Abnormal weight gain typically begins in early childhood and continues to be an issue throughout life. ...

  18. INTEGRATED CLINICAL AND GENETIC APPROACH FOR DIAGNOSIS OF RETT SYNDROME IN CHILDREN

    Directory of Open Access Journals (Sweden)

    I.Yu. Yurov

    2007-01-01

    Full Text Available Rett syndrome represents one of the most important neuropsychiatric genetic diseases. It affects generally girls with the incidence 1:10000–1:15000. Mutations in clinked gene mecp2 are considered as the main cause of the disease. The particular patterns of chromosome x replication (type C are observed in affected females allowing the cytogenetic technique application for the diagnosis. Cytogenetic and molecular genetic studies carried out in the present work allowed us to propose an integrated approach for the diagnosis of this disease. A clinical description, cytogenetic analyses (assessment of an abnormal chromosome X replication type in affected females as well as chromosome complement abnormalities in affected males, molecular cytogenetic assays using DNA probes specific for mecp2 gene region, studying mecp2 mutations, and x chromosome inactivation pattern studies were combined in order to provide the efficient clinical and genetic diagnosis of RTT as well as counseling of family with affected children. The data obtained have shown to increase significantly the efficiency of the diagnosis as well as genetic counseling of families with Rett syndrome affected children.Key words: Rett syndrome, x-chromosome inactivation, mecp2 mutations, replication of chromosome x, children.

  19. SNPs ANALYSIS AS A TOOL IN MOLECULAR GENETICS DIAGNOSTICS

    Directory of Open Access Journals (Sweden)

    Dewi Rusnita

    2015-05-01

    Full Text Available AbstrakSingle Nucleotide Polymorphism (SNP merupakan variasi genetik yang ditemukan pada lebih dari 1% populasi. Haplotipe, yang merupakan sekelompok SNP atau alel dalam satu kromosom, dapat di turunkan ke generasi selanjutnya dan dapat digunakan untuk menelusuri gen penyebab penyakit (marker genetik. Artikel ini bertujuan menjelaskan aplikasi analisis SNP dalam diagnosis beberapa sindrom yang disebabkan gangguan genetik. Berdasarkan laporan studi terdahulu, sindrom yang disebabkan oleh UPD (uniparental disomy maupun penyakit autosomal resesif yang muncul sebagai akibat perkawinan sedarah dapat dideteksi dengan SNP array melalui analisis block of homozygosity dalam kromosom. Kelebihan lain SNP array adalah kemampuannya dalam mendeteksi mosaicism level rendah yang tidak terdeteksi dengan pemeriksaan sitogenetik konvensional. Bahkan saat ini, SNP array sedang diujicobakan dalam IVF untuk mendapatkan bayi yang sehat. Hal ini dapat dilakukan dengan mendeteksi ada atau tidaknya gen tunggal penyebab penyakit pada embrio hasil bayi tabung sebelum embrio ditanamkan ke uterus. Analisis SNP dengan SNP array mempunyai banyak kelebihan dibanding metode pemeriksaan SNP lainnya dan diharapkan dapat digunakan secara luas dalam bidang diagnostik molekuler genetik di masa mendatang.AbstractSingle Nucleotide Polymorphism (SNP is a genetic variant with a frequency of >1% of a large population. Haplotypes, a combination of a set of SNPs/alleles that appear as “associated blocks” on one chromosome, tend to be inherited together to the next offspring and can be used as genetic markers to trace particular diseases. This article aimed at explaining of SNP analysis application in diagnosis of genetic-disorder related syndrome. Previous studies showed that syndromes caused by UPD or autosomal recessive disorder as a result of consanguineous marriage can be identified by SNP array through analysing block of homozygosity region in a chromosome. Another advantage of SNP

  20. Molecular genetic framework for protophloem formation

    Science.gov (United States)

    Rodriguez-Villalon, Antia; Gujas, Bojan; Kang, Yeon Hee; Breda, Alice S.; Cattaneo, Pietro; Depuydt, Stephen; Hardtke, Christian S.

    2014-01-01

    The phloem performs essential systemic functions in tracheophytes, yet little is known about its molecular genetic specification. Here we show that application of the peptide ligand CLAVATA3/EMBRYO SURROUNDING REGION 45 (CLE45) specifically inhibits specification of protophloem in Arabidopsis roots by locking the sieve element precursor cell in its preceding developmental state. CLE45 treatment, as well as viable transgenic expression of a weak CLE45G6T variant, interferes not only with commitment to sieve element fate but also with the formative sieve element precursor cell division that creates protophloem and metaphloem cell files. However, the absence of this division appears to be a secondary effect of discontinuous sieve element files and subsequent systemically reduced auxin signaling in the root meristem. In the absence of the formative sieve element precursor cell division, metaphloem identity is seemingly adopted by the normally procambial cell file instead, pointing to possibly independent positional cues for metaphloem formation. The protophloem formation and differentiation defects in brevis radix (brx) and octopus (ops) mutants are similar to those observed in transgenic seedlings with increased CLE45 activity and can be rescued by loss of function of a putative CLE45 receptor, BARELY ANY MERISTEM 3 (BAM3). Conversely, a dominant gain-of-function ops allele or mild OPS dosage increase suppresses brx defects and confers CLE45 resistance. Thus, our data suggest that delicate quantitative interplay between the opposing activities of BAM3-mediated CLE45 signals and OPS-dependent signals determines cellular commitment to protophloem sieve element fate, with OPS acting as a positive, quantitative master regulator of phloem fate. PMID:25049386

  1. Genetics Home Reference: Chanarin-Dorfman syndrome

    Science.gov (United States)

    ... disease with ichthyosis Triglyceride storage disease with ichthyosis triglyceride storage disease with impaired long-chain fatty acid ... Lipid Metabolism Disorders Genetic and Rare Diseases Information Center (1 ...

  2. Genetic architecture of plasma adiponectin overlaps with the genetics of metabolic syndrome-related traits

    NARCIS (Netherlands)

    P. Henneman (Peter); Y.S. Aulchenko (Yurii); R.R. Frants (Rune); I.V. Zorkoltseva (Irina); M.C. Zillikens (Carola); M. Frölich (Marijke); B.A. Oostra (Ben); J.A.P. Willems van Dijk (Ko); P. Tikka-Kleemola (Päivi)

    2010-01-01

    textabstractOBJECTIVE - Adiponectin, a hormone secreted by adipose tissue, is of particular interest in metabolic syndrome, because it is inversely correlated with obesity and insulin sensitivity. However, it is not known to what extent the genetics of plasma adiponectin and the genetics of obesity

  3. Mouse-based genetic modeling and analysis of Down syndrome

    Science.gov (United States)

    Xing, Zhuo; Li, Yichen; Pao, Annie; Bennett, Abigail S.; Tycko, Benjamin; Mobley, William C.; Yu, Y. Eugene

    2016-01-01

    Introduction Down syndrome (DS), caused by human trisomy 21 (Ts21), can be considered as a prototypical model for understanding the effects of chromosomal aneuploidies in other diseases. Human chromosome 21 (Hsa21) is syntenically conserved with three regions in the mouse genome. Sources of data A review of recent advances in genetic modeling and analysis of DS. Using Cre/loxP-mediated chromosome engineering, a substantial number of new mouse models of DS have recently been generated, which facilitates better understanding of disease mechanisms in DS. Areas of agreement Based on evolutionary conservation, Ts21 can be modeled by engineered triplication of Hsa21 syntenic regions in mice. The validity of the models is supported by the exhibition of DS-related phenotypes. Areas of controversy Although substantial progress has been made, it remains a challenge to unravel the relative importance of specific candidate genes and molecular mechanisms underlying the various clinical phenotypes. Growing points Further understanding of mechanisms based on data from mouse models, in parallel with human studies, may lead to novel therapies for clinical manifestations of Ts21 and insights to the roles of aneuploidies in other developmental disorders and cancers. PMID:27789459

  4. Genetics Home Reference: 5q31.3 microdeletion syndrome

    Science.gov (United States)

    ... up of a patient with 5q31.3 microdeletion syndrome and the smallest de novo 5q31.2q31.3 deletion involving PURA. Mol Cytogenet. 2015 Nov 14;8:89. doi: 10.1186/s13039-015-0193-9. eCollection 2015. ... 5q31.3 Microdeletion syndrome: clinical and molecular characterization of two further cases. ...

  5. Aortic Disease in the Young: Genetic Aneurysm Syndromes, Connective Tissue Disorders, and Familial Aortic Aneurysms and Dissections

    Directory of Open Access Journals (Sweden)

    Marcelo Cury

    2013-01-01

    Full Text Available There are many genetic syndromes associated with the aortic aneurysmal disease which include Marfan syndrome (MFS, Ehlers-Danlos syndrome (EDS, Loeys-Dietz syndrome (LDS, familial thoracic aortic aneurysms and dissections (TAAD, bicuspid aortic valve disease (BAV, and autosomal dominant polycystic kidney disease (ADPKD. In the absence of familial history and other clinical findings, the proportion of thoracic and abdominal aortic aneurysms and dissections resulting from a genetic predisposition is still unknown. In this study, we propose the review of the current genetic knowledge in the aortic disease, observing, in the results that the causative genes and molecular pathways involved in the pathophysiology of aortic aneurysm disease remain undiscovered and continue to be an area of intensive research.

  6. Role for Genetic Anticipation in Lynch Syndrome

    DEFF Research Database (Denmark)

    Nilbert, Mef; Timshel, Susanne; Bernstein, Inge

    2009-01-01

    PURPOSE: Anticipation (ie, an earlier age at onset in successive generations) is linked to repeat expansion in neurodegenerative syndromes, whereas its role in hereditary cancer is unclear. We assessed anticipation in Lynch syndrome (hereditary nonpolyposis colorectal cancer [HNPCC]), in which DNA...... mismatch repair (MMR) defects cause early and accelerated tumor development with a broad tumor spectrum. PATIENTS AND METHODS: In the population-based Danish HNPCC registry, 407 MMR gene mutation carriers who had developed cancer associated with Lynch syndrome, were identified. These individuals formed 290...... parent-child pairs in which age at the first cancer diagnosis was assessed. A paired t-test and a specifically developed bivariate model were used to assess a possible role of anticipation. RESULTS: Both methods revealed anticipation with children developing cancer mean 9.8 years (P

  7. Role for Genetic Anticipation in Lynch Syndrome

    DEFF Research Database (Denmark)

    Nilbert, Mef; Timshel, Susanne; Bernstein, Inge

    2009-01-01

    mismatch repair (MMR) defects cause early and accelerated tumor development with a broad tumor spectrum. PATIENTS AND METHODS: In the population-based Danish HNPCC registry, 407 MMR gene mutation carriers who had developed cancer associated with Lynch syndrome, were identified. These individuals formed 290....... The effect remained when cancers diagnosed at surveillance were excluded, applied to maternal as well as paternal inheritance, and was independent of the MMR gene mutated. CONCLUSION: The effect from anticipation demonstrated in this large, population-based Lynch syndrome cohort underscores the need...

  8. Genetic anticipation in Swedish Lynch syndrome families

    DEFF Research Database (Denmark)

    von Salomé, Jenny; Boonstra, Philip S; Karimi, Masoud

    2017-01-01

    Among hereditary colorectal cancer predisposing syndromes, Lynch syndrome (LS) caused by mutations in DNA mismatch repair genes MLH1, MSH2, MSH6 or PMS2 is the most common. Patients with LS have an increased risk of early onset colon and endometrial cancer, but also other tumors that generally have...... of diagnosis per generation. An alternative analysis using a mixed-effects Cox proportional hazards model (COX-R) estimates a hazard ratio of exp(0.171), or about 1.19, for age of diagnosis between consecutive generations. LS-associated gene-specific anticipation effects are evident for MSH2 (2.6 years...

  9. Phenotypic and molecular genetic analysis of Pyruvate Kinase ...

    African Journals Online (AJOL)

    Phenotypic and molecular genetic analysis of Pyruvate Kinase deficiency in a Tunisian family. Jaouani Mouna, Hamdi Nadia, Chaouch Leila, Kalai Miniar, Mellouli Fethi, Darragi Imen, Boudriga Imen, Chaouachi Dorra, Bejaoui Mohamed, Abbes Salem ...

  10. Genetic diversity and molecular characterization of physic nut ...

    African Journals Online (AJOL)

    ajl

    2013-02-27

    specific genetic ... diversity studies, molecular markers have been applied to identify and to select genotypes with ..... Biologia floral e polinização artificial de pinhão-manso no norte de. Minas Gerais. Pesq. Agropec. Bras.

  11. Molecular Genetic and Gene Therapy Studies of the Musculoskeletal System

    National Research Council Canada - National Science Library

    Baylink, David

    2004-01-01

    The primary goal of the proposed work is to apply several state of the art molecular genetic and gene therapy technologies to address fundamental questions in bone biology with a particular emphasis on attempting: l...

  12. Molecular and Genetic Basis of Stress

    Directory of Open Access Journals (Sweden)

    Bakir Mehić

    2012-05-01

    Full Text Available A person’s reaction to trauma depends on the traumatic situation itself, personality characteristics of the person exposed to trauma, and posttraumatic social environment. Stressor must be extreme event that is extremely dangerous or fatal nature, and which is outside normal human experience [1].Studies investigating psychological consequences of military and civil trauma confirmed the correlation between the nature and intensity of trauma, previous traumatic experience, and psychological consequences. Stress causes the autonomic nervous system hyperactivity. If the stress is extreme or constant symptoms of hyperactivity, increased heart rate, increased respiration, sweating, muscle tension, insomnia and increased anxiety are becoming significant for the prolonging the symptoms of PTSD. Our cells are well adapted to exposure to a mild stress for a short time. In contrast there are potentially serious consequences of exposure to the prolonged stress[2].Various damages arising from the war in Bosnia (1992 - 1995 are almost undetectable, and the consequences for the mental health of the population of Bosnia and Herzegovina are long and painful. It is estimated that in Bosnia and Herzegovina there are 1.75 million people who have some stress-related mental disorders, of which 1 million in the Federation.PTSD may be represented by mutations that must be carried by many genes. There may even be epigenetic reasons for the disorder that have nothing to do with heritable mutations per se. Epigenetic means related to functional changes in the genome that can be regulated by external environmental events that do not involve alterations in the genetic code. One epigenetic mechanism is called “methylation,” a molecular process that affects the activity of a large percentage of genes. Epigenetic investigations say that methylation may be involved in the development of stress regulation in early life[3].A number of longitudinal studies have looked at

  13. NEW MOLECULAR TECHNOLOGIES IN GENETIC DIAGNOSIS OF MALE INFERTILITY

    Directory of Open Access Journals (Sweden)

    V. B. Chernykh

    2017-01-01

    Full Text Available In recent years, the accelerated development of technologies in the field of molecular genetics and cytogenetics has led to significant opportunities of the research and diagnosis of mutations and variations of the genome. This article provides a brief review of new molecular technology, also as the results of their use in reproductive medicine and their perspectives in the genetic diagnosis of male infertility. 

  14. Molecular genetics of hemophilia A: Clinical perspectives

    African Journals Online (AJOL)

    Azza A.G. Tantawy

    incompletely explained by genetic predisposition [71]. The observation of hemophilic monozygotic twins discor- dant for inhibitors points out the interplay of non-genetic fac- tors. Theoretically, challenges of the immune system brought about by infections, vaccinations, and tissue damage in associ- ation with FVIII exposure ...

  15. Molecular Bases and Phenotypic Determinants of Aromatase Excess Syndrome

    Directory of Open Access Journals (Sweden)

    Maki Fukami

    2012-01-01

    Full Text Available Aromatase excess syndrome (AEXS is a rare autosomal dominant disorder characterized by gynecomastia. This condition is caused by overexpression of CYP19A1 encoding aromatase, and three types of cryptic genomic rearrangement around CYP19A1, that is, duplications, deletions, and inversions, have been identified in AEXS. Duplications appear to have caused CYP19A1 overexpression because of an increased number of physiological promoters, whereas deletions and inversions would have induced wide CYP19A1 expression due to the formation of chimeric genes consisting of a noncoding exon(s of a neighboring gene and CYP19A1 coding exons. Genotype-phenotype analysis implies that phenotypic severity of AEXS is primarily determined by the expression pattern of CYP19A1 and the chimeric genes and by the structural property of the fused exons with a promoter function (i.e., the presence or the absence of a natural translation start codon. These results provide novel information about molecular mechanisms of human genetic disorders and biological function of estrogens.

  16. Angelman syndrome: review of clinical and molecular aspects

    Directory of Open Access Journals (Sweden)

    Bird LM

    2014-05-01

    Full Text Available Lynne M Bird1Department of Pediatrics, University of California, Division of Genetics, Rady Children’s Hospital, San Diego, California, USAAbstract: “Angelman syndrome” (AS is a neurodevelopmental disorder whose main features are intellectual disability, lack of speech, seizures, and a characteristic behavioral profile. The behavioral features of AS include a happy demeanor, easily provoked laughter, short attention span, hypermotoric behavior, mouthing of objects, sleep disturbance, and an affinity for water. Microcephaly and subtle dysmorphic features, as well as ataxia and other movement disturbances, are additional features seen in most affected individuals. AS is due to deficient expression of the ubiquitin protein ligase E3A (UBE3A gene, which displays paternal imprinting. There are four molecular classes of AS, and some genotype–phenotype correlations have emerged. Much remains to be understood regarding how insufficiency of E6-AP, the protein product of UBE3A, results in the observed neurodevelopmental deficits. Studies of mouse models of AS have implicated UBE3A in experience-dependent synaptic remodeling.Keywords: Angelman syndrome, chromosome 15q11-13, UBE3A, imprinting

  17. Molecular subtypes and phenotypic expression of Beckwith-Wiedemann syndrome.

    Science.gov (United States)

    Cooper, Wendy N; Luharia, Anita; Evans, Gail A; Raza, Hussain; Haire, Antonita C; Grundy, Richard; Bowdin, Sarah C; Riccio, Andrea; Sebastio, Gianfranco; Bliek, Jet; Schofield, Paul N; Reik, Wolf; Macdonald, Fiona; Maher, Eamonn R

    2005-09-01

    Beckwith-Wiedemann Syndrome (BWS) results from mutations or epigenetic events involving imprinted genes at 11p15.5. Most BWS cases are sporadic and uniparental disomy (UPD) or putative imprinting errors predominate in this group. Sporadic cases with putative imprinting defects may be subdivided into (a) those with loss of imprinting (LOI) of IGF2 and H19 hypermethylation and silencing due to a defect in a distal 11p15.5 imprinting control element (IC1) and (b) those with loss of methylation at KvDMR1, LOI of KCNQ1OT1 (LIT1) and variable LOI of IGF2 in whom there is a defect at a more proximal imprinting control element (IC2). We investigated genotype/epigenotype-phenotype correlations in 200 cases with a confirmed molecular genetic diagnosis of BWS (16 with CDKN1C mutations, 116 with imprinting centre 2 defects, 14 with imprinting centre 1 defects and 54 with UPD). Hemihypertrophy was strongly associated with UPD (Pmanagement and surveillance of BWS children such that screening for Wilms' tumour and hepatoblastoma can be focused on those at highest risk.

  18. Genetics Home Reference: Potocki-Shaffer syndrome

    Science.gov (United States)

    ... and review of the literature. Clin Neuropathol. 2007 Jan-Feb;26(1):1-11. Review. Citation on PubMed Swarr DT, Bloom D, Lewis RA, Elenberg E, Friedman EM, Glotzbach C, Wissman SD, Shaffer LG, Potocki L. Potocki-Shaffer syndrome: comprehensive clinical assessment, review ...

  19. Genetics Home Reference: congenital myasthenic syndrome

    Science.gov (United States)

    ... in this condition. Due to muscle weakness, affected infants may have feeding difficulties. Development of motor skills such as crawling or ... weakness, and delayed development of motor skills. The respiratory problems in congenital myasthenic syndrome result from impaired movement of the muscles of ...

  20. Genetics Home Reference: ring chromosome 14 syndrome

    Science.gov (United States)

    ... learning problems. Development may be delayed, particularly the development of speech and of motor skills such as sitting, standing, and walking. Additional features of ring chromosome 14 syndrome can include slow growth and short stature, a small head ( microcephaly ), puffy hands and/or feet caused ...

  1. Genetics Home Reference: trichorhinophalangeal syndrome type I

    Science.gov (United States)

    ... on PubMed or Free article on PubMed Central Maas S, Shaw A, Bikker H, Hennekam RCM. Trichorhinophalangeal Syndrome. ... nlm.nih.gov/books/NBK425926/ Citation on PubMed Maas SM, Shaw AC, Bikker H, Lüdecke HJ, van ...

  2. Genetics Home Reference: congenital central hypoventilation syndrome

    Science.gov (United States)

    ... Samuels M, Stevens CA, Berry-Kravis EM, Weese-Mayer DE. PHOX2B mutation-confirmed congenital central hypoventilation syndrome: ... Citation on PubMed Axelrod FB, Chelimsky GG, Weese-Mayer DE. Pediatric autonomic disorders. Pediatrics. 2006 Jul;118( ...

  3. Shared genetic factors underlie chronic pain syndromes

    NARCIS (Netherlands)

    Vehof, Jelle; Zavos, Helena M. S.; Lachance, Genevieve; Hammond, Christopher J.; Williams, Frances M. K.

    Chronic pain syndromes (CPS) are highly prevalent in the general population, and increasingly the evidence points to a common etiological pathway. Using a large cohort of twins (n = 8564) characterized for chronic widespread musculoskeletal pain (CWP), chronic pelvic pain (PP), migraine (MIG), dry

  4. Genetics Home Reference: Pitt-Hopkins syndrome

    Science.gov (United States)

    ... 1 link) PubMed OMIM (1 link) PITT-HOPKINS SYNDROME Sources for This Page Amiel J, Rio M, de Pontual L, Redon R, Malan V, Boddaert N, Plouin P, Carter NP, Lyonnet S, Munnich A, Colleaux L. Mutations in TCF4, ... a severe epileptic encephalopathy associated with autonomic dysfunction. ...

  5. Fragile X Syndrome: Genetic Predisposition to Psychopathology.

    Science.gov (United States)

    Bregman, Joel D.; And Others

    1988-01-01

    Psychiatric evaluation of 14 males (ages 3-27 years) with the fragile X syndrome found pervasive hyperactivity, impulsivity, and attentional deficits, and a significant degree of anxiety. However, diagnostic criteria for persistent pervasive developmental disorder and autism were not met. (Author/DB)

  6. Genetics Home Reference: popliteal pterygium syndrome

    Science.gov (United States)

    ... removed. Affected individuals may also have webbing or fusion of the fingers or toes ( syndactyly ), characteristic triangular ... gov/books/NBK1407/ Citation on PubMed More from Genetics Home Reference Bulletins March is Trisomy Awareness Month ...

  7. Genetics Home Reference: Cantú syndrome

    Science.gov (United States)

    ... subunit) of a channel that transports charged potassium atoms (potassium ions) across cell membranes. Mutations in the ... direct-to-consumer genetic testing? What is precision medicine? What is newborn screening? New Pages Obstructive sleep ...

  8. Genetics Home Reference: ankyrin-B syndrome

    Science.gov (United States)

    ... channels are complexes of proteins that transport charged atoms (ions) across cell membranes. In the heart, the ... direct-to-consumer genetic testing? What is precision medicine? What is newborn screening? New Pages Obstructive sleep ...

  9. Genetic Testing for Hereditary Cancer Syndromes

    Science.gov (United States)

    ... complaints about false or misleading health claims in advertisements. The American Society of Human Genetics, a membership ... at the National Institutes of Health FOLLOW US Facebook Twitter Instagram YouTube Google+ LinkedIn GovDelivery RSS CONTACT ...

  10. Genetics Home Reference: Bosma arhinia microphthalmia syndrome

    Science.gov (United States)

    ... literature. BAMS has been found in several different populations. Related Information What information about a genetic condition ... nasal development may affect gonadotropin-releasing hormone (GnRH) neurons, which are nerve cells that control the release ...

  11. Genetics Home Reference: Lesch-Nyhan syndrome

    Science.gov (United States)

    ... condition occurs with a similar frequency in all populations. Related Information What information about a genetic condition ... phosphoribosyl transferase regulates early developmental programming of dopamine neurons: implications for Lesch-Nyhan disease pathogenesis. Hum Mol ...

  12. Genetics Home Reference: PPM-X syndrome

    Science.gov (United States)

    ... who usually have only mild intellectual disability or learning disabilities. Related Information What does it mean if ... Bipolar Disorder Health Topic: Developmental Disabilities Health Topic: Movement Disorders Health Topic: Psychotic Disorders Genetic and Rare Diseases ...

  13. Genetics Home Reference: Cornelia de Lange syndrome

    Science.gov (United States)

    ... excessive body hair (hypertrichosis), an unusually small head ( microcephaly ), hearing loss, and problems with the digestive tract. ... Information & Resources MedlinePlus (3 links) Encyclopedia: Autism Encyclopedia: Microcephaly Health Topic: Developmental Disabilities Genetic and Rare Diseases ...

  14. Genetics Home Reference: Meier-Gorlin syndrome

    Science.gov (United States)

    ... small ears, and, often, an abnormally small head ( microcephaly ). Despite a small head size, most people with ... named? Additional Information & Resources MedlinePlus (2 links) Encyclopedia: Microcephaly Health Topic: Dwarfism Genetic and Rare Diseases Information ...

  15. Genetics Home Reference: Klippel-Feil syndrome

    Science.gov (United States)

    ... navigation Home Page Search Home Health Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Share: Email ... Klimo P Jr, Rao G, Brockmeyer D. Congenital anomalies of the cervical spine. Neurosurg Clin N Am. ...

  16. Genetics Home Reference: Miller-Dieker syndrome

    Science.gov (United States)

    ... Support and Advocacy Resources (2 links) Brain Foundation (Australia) National Organization for Rare Disorders (NORD): Lissencephaly GeneReviews ( ... Pizzardi G, Del Balzo F, Iannetti P. Neuronal migration disorders: clinical, neuroradiologic and genetics aspects. Acta Paediatr. ...

  17. Genetics Home Reference: lymphedema-distichiasis syndrome

    Science.gov (United States)

    ... PubMed Central Mellor RH, Brice G, Stanton AW, French J, Smith A, Jeffery S, Levick JR, Burnand KG, ... 2008.03962.x. Citation on PubMed More from Genetics Home Reference Bulletins March is Trisomy Awareness Month ...

  18. Genetic heterogeneity in Van der Woude syndrome: Identification of ...

    Indian Academy of Sciences (India)

    Priyanka

    Genetic heterogeneity in Van der Woude syndrome: Identification of NOL4 and IRF6 haplotype from the noncoding region as candidates in two families. Priyanka Kumari1, Akhtar Ali2, Subodh Kumar Singh3, Amit Chaurasia4, Rajiva Raman1. 1Cytogenetics Laboratory, Department of Zoology, Institute of Science, Banaras ...

  19. The Prevalence and Phenomenology of Repetitive Behavior in Genetic Syndromes

    Science.gov (United States)

    Moss, Joanna; Oliver, Chris; Arron, Kate; Burbidge, Cheryl; Berg, Katy

    2009-01-01

    We investigated the prevalence and phenomenology of repetitive behavior in genetic syndromes to detail profiles of behavior. The Repetitive Behaviour Questionnaire (RBQ) provides fine-grained identification of repetitive behaviors. The RBQ was employed to examine repetitive behavior in Angelman (N = 104), Cornelia de Lange (N = 101), Cri-du-Chat…

  20. Genetic heterogeneity in Van der Woude syndrome: Identification of ...

    Indian Academy of Sciences (India)

    Priyanka

    IRF6 for VWS and highlights genetic heterogeneity of this disorder, in the Indian population. Key Words: Van der Woude syndrome, NOL4, IRF6, Genome wide linkage, NGS. Introduction. Van der .... down of the mapped regions, linkage was attempted through 15 microsatellite markers from the 3 high LOD regions on ...

  1. Genetics Home Reference: autosomal recessive hyper-IgE syndrome

    Science.gov (United States)

    ... Diseases Health Topic: Pneumonia Health Topic: Skin Infections Genetic and Rare Diseases Information Center (1 link) Autosomal recessive hyper IgE syndrome Additional NIH Resources (2 links) National Institute of Allergy and Infectious Diseases: DOCK8 Deficiency National Institute of Allergy and ...

  2. Genetic Mechanisms Involved in the Phenotype of Down Syndrome

    Science.gov (United States)

    Patterson, David

    2007-01-01

    Down syndrome (DS) is the most common genetic cause of significant intellectual disability in the human population, occurring in roughly 1 in 700 live births. The ultimate cause of DS is trisomy of all or part of the set of genes located on chromosome 21. How this trisomy leads to the phenotype of DS is unclear. The completion of the DNA…

  3. Genetic testing for Lynch syndrome: family communication and motivation

    NARCIS (Netherlands)

    C.H.M. Leenen (Celine); M.D. Heijer (Mariska den); C.A. van der Meer (Conny); E.J. Kuipers (Ernst); M.E. van Leerdam (Monique); A. Wagner (Anja)

    2016-01-01

    textabstractCurrent genetic counselling practice for Lynch syndrome (LS) relies on diagnosed index patients to inform their biological family about LS, referred to as the family-mediated approach. The objective of this study was to evaluate this approach and to identify factors influencing the

  4. Molecular research and genetic engineering of resistance to ...

    African Journals Online (AJOL)

    This paper reviews the recent research progress on genetic methods of resistance, the status and existing problems, traditional breeding, the main resistance mechanism, molecular markers and genetic engineering of resistance genes. It is hoped that new breeding methods and new varieties resistant to Verticillium wilt will ...

  5. Construction of intersubspecific molecular genetic map of lentil

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 91; Issue 3. Construction of intersubspecific molecular genetic map of lentil based on ISSR, RAPD and SSR markers. Mamta Gupta Bhawna Verma Naresh Kumar Rakesh K. Chahota Rajeev Rathour Shyam K. Sharma Sabhyata Bhatia Tilak R. Sharma. Research Article Volume ...

  6. Molecular evaluation of genetic diversity and association studies in ...

    Indian Academy of Sciences (India)

    Molecular evaluation of genetic diversity and association studies in rice. (Oryza sativa L.) C. Vanniarajan, K. K. Vinod and Andy Pereira. J. Genet. 91, 9–19. Table 1. Chromosome-wise distribution of SSR alleles and their number (k), polymorphic information content (PIC) and allele discrimination index (Dm). Chromosome.

  7. Molecular-genetic analysis of two cases with retinoblastoma ...

    Indian Academy of Sciences (India)

    Unknown

    Effective counselling and management of retinoblastoma families using genetic information is presently practised in many parts of the world. We studied histopathological, chromosomal and molecular-genetic data of two retinoblastoma pa- tients from India. The two patients, one with bilateral and the other with unilateral ...

  8. Molecular genetic analysis of grain protein content and flour ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 95; Issue 2. Molecular genetic analysis of grain protein content and flour whiteness degree using RILs in common wheat. XIANYIN SUN KE WU YAN ZHAO ZHAOGUO QIAN FANMEI KONG YING GUO YINGYING WANG SISHEN LI. RESEARCH ARTICLE Volume 95 Issue 2 ...

  9. Molecular-genetic analysis of two cases with retinoblastoma ...

    Indian Academy of Sciences (India)

    Effective counselling and management of retinoblastoma families using genetic information is presently practised in many parts of the world. We studied histopathological, chromosomal and molecular-genetic data of two retinoblastoma patients from India. The two patients, one with bilateral and the other with unilateral ...

  10. Use of molecular genetics and historical records to reconstruct the ...

    African Journals Online (AJOL)

    Recent advances in molecular genetics made the inference of past demographic events through the analysis of gene pools from modern populations possible. The technology uses genetic markers to provide previously unavailable resolution into questions of human evolution, migration and the historical relationship of ...

  11. Diagnostic yield of molecular autopsy in patients with sudden arrhythmic death syndrome using targeted exome sequencing

    DEFF Research Database (Denmark)

    Nunn, Laurence M; Lopes, Luis R; Syrris, Petros

    2016-01-01

    AIMS: The targeted genetic screening of Sudden Arrhythmic Death Syndrome (SADS) probands in a molecular autopsy has a diagnostic yield of up to 35%. Exome sequencing has the potential to improve this yield. The primary aim of this study is to examine the feasibility and diagnostic utility...... previously published rare (0.02-0.5%) candidate mutations-a total yield of 29%. Co-segregation fully confirmed two private SCN5A Na channel mutations. Variants of unknown significance were detected in a further 34% of probands. CONCLUSION: Molecular autopsy using targeted exome sequencing has a relatively...

  12. Micropropagation, genetic engineering, and molecular biology of Populus

    Science.gov (United States)

    N. B. Klopfenstein; Y. W. Chun; M. -S. Kim; M. A. Ahuja; M. C. Dillon; R. C. Carman; L. G. Eskew

    1997-01-01

    Thirty-four Populus biotechnology chapters, written by 85 authors, are comprised in 5 sections: 1) in vitro culture (micropropagation, somatic embryogenesis, protoplasts, somaclonal variation, and germplasm preservation); 2) transformation and foreign gene expression; 3) molecular biology (molecular/genetic characterization); 4) biotic and abiotic resistance (disease,...

  13. Hereditary hemorrhagic telangiectasia clinical and molecular genetics

    NARCIS (Netherlands)

    Letteboer, T.G.W.

    2010-01-01

    Hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber (ROW) syndrome is an autosomal dominant disease characterized by vascular malformations in multiple organ systems. HHT has an age-related penetrance and variable clinical expression. The clinical symptoms are caused by direct

  14. Genetic anticipation in Swedish Lynch syndrome families

    DEFF Research Database (Denmark)

    von Salomé, Jenny; Boonstra, Philip S; Karimi, Masoud

    2017-01-01

    Among hereditary colorectal cancer predisposing syndromes, Lynch syndrome (LS) caused by mutations in DNA mismatch repair genes MLH1, MSH2, MSH6 or PMS2 is the most common. Patients with LS have an increased risk of early onset colon and endometrial cancer, but also other tumors that generally have......-2013. We analyzed a homogenous group of mutation carriers, utilizing information from both affected and non-affected family members. In total, 239 families with a mismatch repair gene mutation (96 MLH1 families, 90 MSH2 families including one family with an EPCAM-MSH2 deletion, 39 MSH6 families, 12 PMS2...... of diagnosis per generation. An alternative analysis using a mixed-effects Cox proportional hazards model (COX-R) estimates a hazard ratio of exp(0.171), or about 1.19, for age of diagnosis between consecutive generations. LS-associated gene-specific anticipation effects are evident for MSH2 (2.6 years...

  15. Kartagener Syndrome: A Rare Genetic Disorder

    Directory of Open Access Journals (Sweden)

    Kunjan Shakya

    2009-01-01

    Full Text Available Kartagener Syndrome is a rare autosomal recessive disorder consisting of triad of sinusitis, bronchiectasis and situs inversus with dextrocardia. It is the subset of disorder called primary ciliary dyskinesia in which the cilia have abnormal structure and/or function resulting in multisystem diseases of various severity. Clinical manifestations include lifelong, chronic upper and lower respiratory tract diseases secondary to ineffective mucociliary clearance. Early diagnosis and management of chest infections can prevent irreversible damage to lungs and prevent potential lifelong complications. This case report is on a patient who presented with long standing history of sinusitis, bronchiectasis and on examination situs inversus with dextrocardia. Key Words:bronchiectasis, dextrocardia, kartagener syndrome, primary ciliary dyskinesia, situs inversus

  16. RESEARCH NOTE Molecular genetic analysis of consanguineous ...

    Indian Academy of Sciences (India)

    Navya

    Department of Biotechnology & Genetic Engineering, Kohat University of. Science & Technology, Kohat, Khyber Pakhtunkhwa, Pakistan. 7. Diagnostic Genomic Division, Department of Laboratory Medicine & Pathology,. Hamad Medical Corporation, Doha, 3050, Qatar. * These authors have equally contributed in this work.

  17. Molecular and genetic study of wheat rusts

    African Journals Online (AJOL)

    Nicholas Le Maitre

    Phylogenetic trees were created for leaf and stem rust pathotypes. Field isolates of ... Key words: Prevalence, microsatellite, amplified fragment length polymorphisms (AFLP), phylogeny, Puccinia. INTRODUCTION. Puccinia triticina Eriks ..... Genetic distances and reconstruction phylogenetic trees from microsatellite DNA.

  18. Genetically complex epilepsies, copy number variants and syndrome constellations.

    Science.gov (United States)

    Mefford, Heather C; Mulley, John C

    2010-10-05

    Epilepsy is one of the most common neurological disorders, with a prevalence of 1% and lifetime incidence of 3%. There are numerous epilepsy syndromes, most of which are considered to be genetic epilepsies. Despite the discovery of more than 20 genes for epilepsy to date, much of the genetic contribution to epilepsy is not yet known. Copy number variants have been established as an important source of mutation in other complex brain disorders, including intellectual disability, autism and schizophrenia. Recent advances in technology now facilitate genome-wide searches for copy number variants and are beginning to be applied to epilepsy. Here, we discuss what is currently known about the contribution of copy number variants to epilepsy, and how that knowledge is redefining classification of clinical and genetic syndromes.

  19. Genetic predisposition syndromes and their management.

    Science.gov (United States)

    Euhus, David M; Robinson, Linda

    2013-04-01

    Apart from BRCA1, BRCA2, and TP53, more than a dozen breast cancer susceptibility genes have been identified. Recognizing affected individuals depends on evaluation of cancer family history and recognition of certain phenotypic markers on physical examination. Genetic testing provides a powerful tool for individualized risk stratification. Mutation carriers have several options for managing risk, including lifestyle alterations, enhanced surveillance, chemoprevention, and prophylactic surgery. Genetic counseling and testing should be considered in the initial evaluation of patients with newly diagnosed breast cancer because this information contributes to surgical decisions, radiation therapy options, and systemic therapy choices. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Clinical and molecular phenotype of Aicardi-Goutieres syndrome

    NARCIS (Netherlands)

    Rice, Gillian; Patrick, Teresa; Parmar, Rekha; Taylor, Claire F.; Aeby, Alec; Aicardi, Jean; Artuch, Rafael; Montalto, Simon Attard; Bacino, Carlos A.; Barroso, Bruno; Baxter, Peter; Benko, Willam S.; Bergmann, Carsten; Bertini, Enrico; Biancheri, Roberta; Blair, Edward M.; Blau, Nenad; Bonthron, David T.; Briggs, Tracy; Brueton, Louise A.; Brunner, Han G.; Burke, Christopher J.; Carr, Ian M.; Carvalho, Daniel R.; Chandler, Kate E.; Christen, Hans-Jurgen; Corry, Peter C.; Cowan, Frances M.; Cox, Helen; D'Arrigo, Stefano; Dean, John; de Laet, Corinne; de Praeter, Claudine; Dery, Catherine; Ferrie, Colin D.; Flintoff, Kim; Frints, Suzanna G. M.; Garcia-Cazorla, Angels; Gener, Blanca; Goizet, Cyril; Goutieres, Francoise; Green, Andrew J.; Guet, Agnes; Hamel, Ben C. J.; Hayward, Bruce E.; Heiberg, Arvid; Hennekam, Raoul C.; Husson, Marie; Jackson, Andrew P.; Jayatunga, Rasieka; Jiang, Yong-Hui; Kant, Sarina G.; Kao, Amy; King, Mary D.; Kingston, Helen M.; Klepper, Joerg; van der Knaap, Marjo S.; Kornberg, Andrew J.; Kotzot, Dieter; Kratzer, Wilfried; Lacombe, Didier; Lagae, Lieven; Landrieu, Pierre Georges; Lanzi, Giovanni; Leitch, Andrea; Lim, Ming J.; Livingston, John H.; Lourenco, Charles M.; Lyall, E. G. Hermione; Lynch, Sally A.; Lyons, Michael J.; Marom, Daphna; McClure, John P.; McWilliam, Robert; Melancon, Serge B.; Mewasingh, Leena D.; Moutard, Marie-Laure; Nischal, Ken K.; Ostergaard, John R.; Prendiville, Julie; Rasmussen, Magnhild; Rogers, R. Curtis; Roland, Dominique; Rosser, Elisabeth M.; Rostasy, Kevin; Roubertie, Agathe; Sanchis, Amparo; Schiffmann, Raphael; Scholl-Burgi, Sabine; Seal, Sunita; Shalev, Stavit A.; Corcoles, C. Sierra; Sinha, Gyan P.; Soler, Doriette; Spiegel, Ronen; Stephenson, John B. P.; Tacke, Uta; Tan, Tiong Yang; Till, Marianne; Tolmie, John L.; Tomlin, Pam; Vagnarelli, Federica; Valente, Enza Maria; van Coster, Rudy N. A.; van der Aa, Nathalie; Vanderver, Adeline; Vles, Johannes S. H.; Voit, Thomas; Wassmer, Evangeline; Weschke, Bernhard; Whiteford, Margo L.; Willemsen, Michel A. A.; Zankl, Andreas; Zuberi, Sameer M.; Orcesi, Simona; Fazzi, Elisa; Lebon, Pierre; Crow, Yanick J.

    2007-01-01

    Aicardi-Goutieres syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3'-->5' exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease

  1. Genetic Analysis of 'PAX6-Negative' Individuals with Aniridia or Gillespie Syndrome

    DEFF Research Database (Denmark)

    Ansari, Morad; Rainger, Jacqueline; Hanson, Isabel M

    2016-01-01

    We report molecular genetic analysis of 42 affected individuals referred with a diagnosis of aniridia who previously screened as negative for intragenic PAX6 mutations. Of these 42, the diagnoses were 31 individuals with aniridia and 11 individuals referred with a diagnosis of Gillespie syndrome......) to PAX6 and one within a gene desert 5' (telomeric) to PITX2. Sequence analysis of the FOXC1 and PITX2 coding regions identified two plausibly pathogenic de novo FOXC1 missense mutations (p.Pro79Thr and p.Leu101Pro). No intragenic mutations were detected in PITX2. FISH mapping in an individual...... with Gillespie-like syndrome with an apparently balanced X;11 reciprocal translocation revealed disruption of a gene at each breakpoint: ARHGAP6 on the X chromosome and PHF21A on chromosome 11. In the other individuals with Gillespie syndrome no mutations were identified in either of these genes, or in HCCS...

  2. Genetics Home Reference: triple X syndrome

    Science.gov (United States)

    ... in cell division called nondisjunction can result in reproductive cells with an abnormal number of chromosomes. For example, an egg or sperm cell may gain an extra copy of the X ... nondisjunction. If one of these atypical reproductive cells contributes to the genetic makeup of a ...

  3. Molecular genetics and gene expression in atherosclerosis

    NARCIS (Netherlands)

    Doevendans, P. A.; Jukema, W.; Spiering, W.; Defesche, J. C.; Kastelein, J. J.

    2001-01-01

    Although molecular cardiology is a relative young discipline, the impact of the new techniques on diagnosis and therapy in cardiovascular disease are extensive. Our insight into pathophysiological mechanisms is rapidly expanding and is changing our understanding of cardiovascular disease radically

  4. Molecular and Genetic Basis of Hereditary Connective-Tissue Diseases Accompanied by Frequent Fractures

    Directory of Open Access Journals (Sweden)

    G. T. Yakhyaeva

    2016-01-01

    Full Text Available Frequent bone fractures in infancy require the elimination of a large number (> 100 of genetic disorders. The modern diagnostic method of hereditary diseases characterized by debilitating course is a new generation sequencing. The article presents the results of molecular-genetic study conducted in 18 patients with clinical symptoms of connective tissue disorders. 10 (56% patients had mutations in the genes encoding type I collagen chains, leading to the development of osteogenesis imperfecta, 5 (28% — mutations in IV and V type collagen genes that are responsible for the development of Ehlers-Danlos syndrome. 3 (17% patients had mutations in the gene encoding fibrillin-1 protein, deficiency of which is manifested by Marfan syndrome. However, the correlation between patient's phenotype and discovered mutations in the investigated gene is established not in all cases.

  5. Clinicopathologic, Immunohistochemical, and Molecular Features of Histiocytoid Sweet Syndrome.

    Science.gov (United States)

    Alegría-Landa, Victoria; Rodríguez-Pinilla, Socorro María; Santos-Briz, Angel; Rodríguez-Peralto, José Luis; Alegre, Victor; Cerroni, Lorenzo; Kutzner, Heinz; Requena, Luis

    2017-07-01

    Histiocytoid Sweet syndrome is a rare histopathologic variant of Sweet syndrome. The nature of the histiocytoid infiltrate has generated considerable controversy in the literature. The main goal of this study was to conduct a comprehensive overview of the immunohistochemical phenotype of the infiltrate in histiocytoid Sweet syndrome. We also analyze whether this variant of Sweet syndrome is more frequently associated with hematologic malignancies than classic Sweet syndrome. This is a retrospective case series study of the clinicopathologic, immunohistochemical, and molecular features of 33 patients with a clinicopathologic diagnosis of histiocytoid Sweet syndrome was conducted in the dermatology departments of 5 university hospitals and a private laboratory of dermatopathology. The clinical, histopathological, immunohistochemical, and follow-up features of 33 patients with histiocytoid Sweet syndrome were analyzed. In some cases, cytogenetic studies of the dermal infiltrate were also performed. We compare our findings with those of the literature. The dermal infiltrate from the 33 study patients (20 female; median age, 49 years; age range, 5-93 years; and 13 male; median age, 42 years; age range, 4-76 years) was mainly composed of myeloperoxidase-positive immature myelomonocytic cells with histiocytoid morphology. No cytogenetic anomalies were found in the infiltrate except in 1 case in which neoplastic cells of chronic myelogenous leukemia were intermingled with the cells of histiocytoid Sweet syndrome. Authentic histiocytes were also found in most cases, with a mature immunoprofile, but they appeared to be a minor component of the infiltrate. Histiocytoid Sweet syndrome was not more frequently related with hematologic malignancies than classic neutrophilic Sweet syndrome. The dermal infiltrate of cutaneous lesions of histiocytoid Sweet syndrome is composed mostly of immature cells of myeloid lineage. This infiltrate should not be interpreted as leukemia cutis.

  6. Familial clustering of Leiomyomatosis peritonealis disseminata: an unknown genetic syndrome?

    Directory of Open Access Journals (Sweden)

    Daboul Isam

    2005-10-01

    Full Text Available Abstract Background Leiomyomatosis peritonealis disseminata (LPD is defined as the occurrence of multiple tumorous intraabdominal lesions, which are myomatous nodules. LPD is a rare disease with only about 100 cases reported. The usual course of LPD is benign with the majority of the patients being premenopausal females. Only two cases involving men have been reported, no syndrome or familial occurrence of LPD has been described. Case presentation We describe a Caucasian-American family in which six members (three men are diagnosed with Leiomyomatosis peritonealis disseminata (LPD and three deceased family members most likely had LPD (based on the autopsy reports. Furthermore we describe the association of LPD with Raynaud's syndrome and Prurigo nodularis. Conclusion Familial clustering of Leiomyomatosis peritonealis disseminata (LPD has not been reported so far. The etiology of LPD is unknown and no mode of inheritance is known. We discuss possible modes of inheritance in the presented case, taking into account the possibility of a genetic syndrome. Given the similarity to other genetic syndromes with leiomyomatosis and skin alterations, we describe possible similar genetic pathomechanisms.

  7. Freeman–Sheldon Syndrome: First Molecularly Confirmed Case from Sub-Saharan Africa

    Directory of Open Access Journals (Sweden)

    A. M. Ali

    2017-01-01

    Full Text Available We report a case of a male baby who has characteristic signs of Freeman–Sheldon syndrome, a rare but recognizable, severe autosomal dominant form of distal arthrogryposis. Diagnosis was based on the distinctive clinical characteristics of the syndrome and confirmed by genetic analysis that showed a de novo missense mutation c.2015G>A (p.Arg672His of the MYH3 gene. We highlight the different features present in our patient and describe the etiology of the Freeman–Sheldon phenotype and how its clinical complications can be dealt with. To the best of our knowledge, this is the first molecularly confirmed case of Freeman–Sheldon syndrome in sub-Saharan Africa.

  8. Next generation sequencing for molecular confirmation of hereditary sudden cardiac death syndromes.

    Science.gov (United States)

    Márquez, Manlio F; Cruz-Robles, David; Ines-Real, Selene; Vargas-Alarcón, Gilberto; Cárdenas, Manuel

    2015-01-01

    Hereditary sudden cardiac death syndromes comprise a wide range of diseases resulting from alteration in cardiac ion channels. Genes involved in these syndromes represent diverse mutations that cause the altered encoding of the diverse proteins constituting these channels, thus affecting directly the currents of the corresponding ions. In the present article we will briefly review how to arrive to a clinical diagnosis and we will present the results of molecular genetic studies made in Mexican subjects attending the SCD Syndromes Clinic of the National Institute of Cardiology of Mexico City. Copyright © 2014 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

  9. Metabolic syndrome: clinical concept and molecular basis.

    Science.gov (United States)

    Funahashi, Tohru; Matsuzawa, Yuji

    2007-01-01

    The metabolic syndrome is a cluster of insulin resistance, elevated blood pressure, and atherogenic dyslipidemia and is a common basis of cardiovascular diseases (CVD). Although the precise mechanism remains to be elucidated, a practical definition is needed. A worldwide definition that considers increased waist circumference as an essential component has been settled. Visceral fat locates upstream of the liver. Free fatty acids and glycerol derived from visceral fat reach the liver and stimulate lipoprotein synthesis and gluconeogenesis, respectively. The adipose tissue produces a variety of bioactive substances conceptualized as 'adipocytokines'. Overproduction of plasminogen activator inhibitor-1 and tumor necrosis factor- seems to relate to the thrombotic and inflammatory tendency. On the other hand, adiponectin, which has antiatherogenic and antidiabetic activities, is reduced in subjects with metabolic syndrome. In Japan, the waist circumference criterion based on visceral fat accumulation has been adopted. The concept of this syndrome has been widely publicized, and health promotion programs based on the concept have commenced in various areas of the country. Such 'Adipo-Do-It' movement is an incentive to encourage physical exercise to reduce visceral fat and is a big challenge to prevent life-style-related diseases and CVD.

  10. The genetic component of Brugada syndrome

    DEFF Research Database (Denmark)

    Nielsen, Morten; Holst, Anders G; Olesen, Søren Peter

    2013-01-01

    . The prevalence varies with ethnicity ranging from 1:2,000 to 1:100,000 in different parts of the world. Today, hundreds of variants in 17 genes have been associated with BrS of which mutations in SCN5A, coding for the cardiac voltage-gated sodium channel, accounts for the vast majority. Despite this......, approximately 70% of BrS cases cannot be explained genetically with the current knowledge. Moreover, the monogenic role of some of the variants previously described as being associated with BrS has been questioned by their occurrence in about 4% (1:23) of the general population as found in NHLBI GO Exome......-defibrillator (ICD). The risk stratification and indications for ICD treatment are based on the ECG and on the clinical and family history. In this review we discuss the genetic basis of BrS....

  11. Establishment of the first WHO international genetic reference panel for Prader Willi and Angelman syndromes.

    Science.gov (United States)

    Boyle, Jennifer; Hawkins, Malcolm; Barton, David E; Meaney, Karen; Guitart, Miriam; O'Grady, Anna; Tobi, Simon; Ramsden, Simon C; Elles, Rob; Gray, Elaine; Metcalfe, Paul; Hawkins, J Ross

    2011-08-01

    Prader Willi and Angelman syndromes are clinically distinct genetic disorders both mapping to chromosome region 15q11-q13, which are caused by a loss of function of paternally or maternally inherited genes in the region, respectively. With clinical diagnosis often being difficult, particularly in infancy, confirmatory genetic diagnosis is essential to enable clinical intervention. However, the latter is challenged by the complex genetics behind both disorders and the unmet need for characterised reference materials to aid accurate molecular diagnosis. With this in mind, a panel of six genotyping reference materials for Prader Willi and Angelman syndromes was developed, which should be stable for many years and available to all diagnostic laboratories. The panel comprises three Prader Willi syndrome materials (two with different paternal deletions, and one with maternal uniparental disomy (UPD)) and three Angelman syndrome materials (one with a maternal deletion, one with paternal UPD or an epigenetic imprinting centre defect, and one with a UBE3A point mutation). Genomic DNA was bulk-extracted from Epstein-Barr virus-transformed lymphoblastoid cell lines established from consenting patients, and freeze-dried as aliquots in glass ampoules. In total, 37 laboratories from 26 countries participated in a collaborative study to assess the suitability of the panel. Participants evaluated the blinded, triplicate materials using their routine diagnostic methods against in-house controls or externally sourced uncertified reference materials. The panel was established by the Expert Committee on Biological Standardization of the World Health Organization as the first International Genetic Reference Panel for Prader Willi and Angelman syndromes.

  12. Tetrasomy 21 pter {yields} q22.1 and Down syndrome: Molecular definition of the region

    Energy Technology Data Exchange (ETDEWEB)

    Daumer-Haas, C.; Schuffenhauer, S.; Walther, J.U. [Universitaet Muenchen (Germany); Portsmann, T. [Humboldt Universitaet, Berlin (Germany); Korenberg, J.R.; Schipper, R.D. [Univ. of California, Los Angeles, CA (United States)

    1994-12-01

    Down syndrome is usually caused by complete trisomy 21. Rarely, it is due to partial trisomy of the segment 21q22. We report on a 33-month-old girl with tetrasomy 21 pter {yields} q22.1 resulting from an extra chromosome idic(21)(q22.1). She has craniofacial traits typical of Down syndrome, including brachycephaly, third fontanel, upward slanting palpebral fissures, round face, and protruding tongue. Speech development is quite delayed whereas motor development is only mildly retarded. The molecular content of the extra isodicentric chromosome was defined by molecular genetic investigations using 13 single copy probes unique to chromosome 21, and SOD1 expression studies. The child was found to have 4 copies of the region defined by D21S16 (21cen) through D21S93 on 21q22.1 and two copies of the remaining region defined by SOD1 {yields} D21S55 {yields} D21S123. In view of the recent assignment of Down syndrome facial characters to the 21q22 region, defined in part by D21S55, it is significant that this child shows a subset of Down syndrome facial manifestations, without duplication of this region. These results suggest that genes contributing to the facial and some of the hand manifestations of Down syndrome also exist in the chromosomal region proximal to D21S55 in band 21q22.1. 34 refs., 6 figs., 3 tabs.

  13. Molecular diversity and genetic relationships in Secale

    Indian Academy of Sciences (India)

    Department of Genetics and Biotechnology, University of Trás-os-Montes and Alto Douro, Quinta de Prados, 5001-801 Vila Real, Portuga; BioISI- Biosystems & Integrative Sciences Institute, University of Lisboa, Faculty of Sciences, Campo Grande, Lisboa, Portugal; Departamento de Genética, Facultad de Biologia, ...

  14. Molecular taxonomic, epidemiological and population genetic ...

    African Journals Online (AJOL)

    Admin

    Sexual recombination is a likely mechanism contributing to the high genetic diversity of C. gloeosporioides in yam-based cropping systems. Studies have been initiated to understand the mechanisms that generate ... our knowledge, this is the only review of advances in yam ...... Kuala Lumpur, Malaysia, pp 67-69. Singh RD ...

  15. RESEARCH NOTE Molecular genetic analysis of consanguineous ...

    Indian Academy of Sciences (India)

    Navya

    proteins are involved in cell cycle and its regulation. Herein the present clinical genetic study, we present two consanguineous Pakistani families segregating primary microcephaly and intellectual disability. These families were ascertained from the Saraiki ethnic part of. Khyber-Pukhtunkhwa province in Pakistan.

  16. Molecular diversity and genetic relationships in Secale

    Indian Academy of Sciences (India)

    Over the years, there has been much controversy about the taxonomy of the Secale genus. ... have become routine in plant biotechnology, such as genetic diversity studies. ISSR (Zietkiewicz et al. 1994) and ... 1996) were not amplified in the bulk DNA samples. The number of plants used to construct the bulk samples was.

  17. Molecular diversity and genetic relationships in Secale

    Indian Academy of Sciences (India)

    1Department of Genetics and Biotechnology, University of Trás-os-Montes and Alto Douro, Quinta de Prados,. 5001-801 Vila Real, Portugal. 2Departamento de Genética, Facultad de Biologia, Universidad Complutense, C/ José Antonio Novais, 12,. 28040 Madrid, Spain. 3BioISI- Biosystems & Integrative Sciences Institute, ...

  18. Molecular markers: a potential resource for ginger genetic diversity studies.

    Science.gov (United States)

    Ismail, Nor Asiah; Rafii, M Y; Mahmud, T M M; Hanafi, M M; Miah, Gous

    2016-12-01

    Ginger is an economically important and valuable plant around the world. Ginger is used as a food, spice, condiment, medicine and ornament. There is available information on biochemical aspects of ginger, but few studies have been reported on its molecular aspects. The main objective of this review is to accumulate the available molecular marker information and its application in diverse ginger studies. This review article was prepared by combing material from published articles and our own research. Molecular markers allow the identification and characterization of plant genotypes through direct access to hereditary material. In crop species, molecular markers are applied in different aspects and are useful in breeding programs. In ginger, molecular markers are commonly used to identify genetic variation and classify the relatedness among varieties, accessions, and species. Consequently, it provides important input in determining resourceful management strategies for ginger improvement programs. Alternatively, a molecular marker could function as a harmonizing tool for documenting species. This review highlights the application of molecular markers (isozyme, RAPD, AFLP, SSR, ISSR and others such as RFLP, SCAR, NBS and SNP) in genetic diversity studies of ginger species. Some insights on the advantages of the markers are discussed. The detection of genetic variation among promising cultivars of ginger has significance for ginger improvement programs. This update of recent literature will help researchers and students select the appropriate molecular markers for ginger-related research.

  19. Silent angels the genetic and clinical aspects of Rett syndrome

    Directory of Open Access Journals (Sweden)

    Dziwota Ewelina

    2016-12-01

    Full Text Available Rett syndrome is a neurodevelopmental genetic disorder and, because of some behavioral characteristics, individuals affected by the disease are known as silent angels. Girls with Rett syndrome perform stereotyped movements, they have learning difficulties, their reaction time is prolonged, and they seem alienated in the environment. These children require constant pediatric, neurological and orthopedic care. In the treatment of Rett syndrome physical therapy, music therapy, hydrotherapy, hippotherapy, behavioral methods, speech therapy and diet, are also used. In turn, psychological therapy of the syndrome is based on the sensory integration method, using two or more senses simultaneously. In 80% of cases, the syndrome is related to mutations of the MECP2 gene, located on chromosome X. The pathogenesis of Rett syndrome is caused by the occurrence of a non-functional MeCP2 protein, which is a transcription factor of many genes, i.e. Bdnf, mef2c, Sgk1, Uqcrc1. Abnormal expression of these genes reveals a characteristic disease phenotype. Clinical symptoms relate mainly to the nervous, respiratory, skeletal and gastrointestinal systems. Currently causal treatment is not possible. However, researchers are developing methods by which, perhaps in the near future, it will be possible to eliminate the mutations in the MECP2 gene, and this will give a chance to the patient for normal functioning.

  20. Brazilian Nelore cattle: a melting pot unfolded by molecular genetics.

    Science.gov (United States)

    Dani, M A C; Heinneman, M B; Dani, S U

    2008-10-21

    The aim of the present article was to study the population structure and genetic diversity of Nelore cattle and genetic relationships between Nelore and different taurine and zebu breeds raised in Brazil. DNA polymorphism analysis was carried out with 1976 animals of 16 zebu, taurine and synthetic breeds raised in Brazil. A higher genetic differentiation was observed in taurine than in zebu cattle. Gene flow was intense between the different zebu populations. Genetic affinity analysis within the most conspicuous Brazilian zebu beef cattle, the Nelore, was carried out in a group of 615 animals from 15 representative herds. This analysis revealed at least two major Nelore subtypes, named after some genotype-phenotype associations such as the "thrifty type" and the "demanding type". This study provides molecular genetic evidence that, despite selection based on the phenotype, gene flow and gene segregation still play a major role in maintaining genetic variability within the Nelore and zebu population as a whole in Brazil.

  1. Genetic breeding of silkworms: from traditional hybridization to molecular design.

    Science.gov (United States)

    Ma, San-Yuan; Xia, Qing-You

    2017-11-20

    Sericulture is one of the great inventions of the Chinese people and has become an important cultural feature of China. As China is the long-lasting center of silk production, genetic breeding of silkworm was highly developed historically, and has formed a comprehensive system for breeding and preservation of new varieties. However, silkworm breeding reached a bottleneck recently, because most of the traditional genetic resources have been utilized and silkworm strains have become homogeneous. Meanwhile, sericulture in China meets huge challenges in the 21 st century. In recent years, with the development and rapid application of molecular biology, genomics, transgene and genome editing, silkworm genetic breeding has entered a new era. In this review, we summarize the development of silkworm genetic breeding, especially the progress and perspective of transgene and genome editing in genetic engineering of silkworms. We also discuss the future development of silkworm genetic breeding.

  2. Molecular discrimination and genetic relationships between some ...

    African Journals Online (AJOL)

    Cucurbita pepo ssp. pepo; zucchini group is a widely grown and economically important group belonging to genus Cucurbita, and being one of the easiest groups to cultivate in temperate climate with overwhelming production. Since, RAPD analysis provides a fast and reliable method for molecular characterization and ...

  3. Molecular markers unravel intraspecific and interspecific genetic ...

    Indian Academy of Sciences (India)

    2011). However, to develop efficient interspecific crosses it is essential to determine their phy- logenetic relationships. Although some workers have tried nuclear ribosomal DNA internal transcribed spacer (ITS) regions for this purpose (Ronsted et al. 2002; Dhar et al. 2006), it would be worthwhile to use molecular markers,.

  4. Oligocone trichromacy: clinical and molecular genetic investigations

    DEFF Research Database (Denmark)

    Andersen, Mette K G; Christoffersen, Nynne L B; Sander, Birgit

    2010-01-01

    of unknown significance in CNGB3 and PDE6C in two other patients. CONCLUSIONS: Oligocone trichromacy is a heterogeneous condition with respect to both phenotypic appearance and genetic background. The finding of mutations in genes known to be involved in complete and incomplete achromatopsia supports...... the notion that some forms of OT is an extreme form of incomplete achromatopsia with preferential loss of peripheral cones....

  5. Genetic basis of dental agenesis--molecular genetics patterning clinical dentistry.

    Science.gov (United States)

    Chhabra, N; Goswami, M; Chhabra, A

    2014-03-01

    Tooth agenesis is one of the most common congenital malformations in humans. Hypodontia can either occur as an isolated condition (non-syndromic hypodontia) or can be associated with a syndrome (syndromic hypodontia), highlighting the heterogeneity of the condition. Though much progress has been made to identify the developmental basis of tooth formation, knowledge of the etiological basis of inherited tooth loss is still lacking. To date, the mutation spectra of non-syndromic form of familial and sporadic tooth agenesis in humans have revealed defects in various such genes that encode transcription factors, MSX1 and PAX9 or genes that code for a protein involved in canonical Wnt signaling (AXIN2), and a transmembrane receptor of fibroblast growth factors (FGFR1). The aim of this paper is to review the current literature on the molecular mechanisms responsible for selective hypodontia in humans and to present a detailed overview of causative genes and syndromes associated with hypodontia.

  6. Molecular and Genetic Determinants of Glioma Cell Invasion

    Directory of Open Access Journals (Sweden)

    Kenta Masui

    2017-12-01

    Full Text Available A diffusely invasive nature is a major obstacle in treating a malignant brain tumor, “diffuse glioma”, which prevents neurooncologists from surgically removing the tumor cells even in combination with chemotherapy and radiation. Recently updated classification of diffuse gliomas based on distinct genetic and epigenetic features has culminated in a multilayered diagnostic approach to combine histologic phenotypes and molecular genotypes in an integrated diagnosis. However, it is still a work in progress to decipher how the genetic aberrations contribute to the aggressive nature of gliomas including their highly invasive capacity. Here we depict a set of recent discoveries involving molecular genetic determinants of the infiltrating nature of glioma cells, especially focusing on genetic mutations in receptor tyrosine kinase pathways and metabolic reprogramming downstream of common cancer mutations. The specific biology of glioma cell invasion provides an opportunity to explore the genotype-phenotype correlation in cancer and develop novel glioma-specific therapeutic strategies for this devastating disease.

  7. Can EEG Differentiate Among Syndromes in Genetic Generalized Epilepsy?

    Science.gov (United States)

    Seneviratne, Udaya; Hepworth, Graham; Cook, Mark; DʼSouza, Wendyl

    2017-05-01

    To evaluate EEG differences among syndromes in genetic generalized epilepsy based on quantified data. Twenty-four-hour ambulatory EEGs were recorded in consecutive patients diagnosed with genetic generalized epilepsy. All epileptiform EEG abnormalities were quantified into density scores (total duration of epileptiform discharges per hour). One-way analysis of variance was conducted to find out differences in EEG density scores among the syndromes. Generalized linear mixed models were also fitted to explore the association between the proportion of "pure" generalized spike-wave paroxysms and fragments (without intervening polyspikes/polyspike-waves) and the syndromes. In total, 6,923 epileptiform discharges were analyzed from 105 abnormal EEGs. In the analysis of variance, six EEG variables were significantly different among syndromes: total spike density (P = 0.001), total polyspike and polyspike-wave density (P = 0.049), generalized spike-wave-only density (P paroxysm density (P paroxysm duration mean (P = 0.018), and generalized paroxysm duration maximum (P = 0.009). The density of epileptiform discharges and the paroxysm durations were the highest in juvenile absence epilepsy followed by juvenile myoclonic epilepsy, childhood absence epilepsy, and generalized epilepsy with tonic-clonic seizures only. Generalized linear mixed models revealed that "pure" generalized spike-wave discharges (without intervening polyspikes/polyspike waves) tended to be more frequent in absence epilepsies, although the difference was not statistically significant (P = 0.21). The findings of this study suggest that the density and duration of epileptiform discharges can help differentiate among genetic generalized epilepsy syndromes.

  8. Genetic, Clinical, and Laboratory Markers for DOCK8 Immunodeficiency Syndrome

    Directory of Open Access Journals (Sweden)

    Jeremiah C. Davis

    2010-01-01

    Full Text Available DOCK8 immunodeficiency syndrome (DIDS is a combined immunodeficiency characterized by recurrent viral infections, severe atopy, and early onset malignancy. Genetic studies revealed large, unique deletions in patients from different families and ethnic backgrounds. Clinical markers of DIDS include atopic dermatitis, allergies, cutaneous viral infections, recurrent respiratory tract infections, and malignancy. Immune assessments showed T cell lymphopenia, hyper-IgE, hypo-IgM, and eosinophilia. The impaired lymphocyte functions in DIDS patients appear central for disease pathogenesis.

  9. Primer on molecular genetics. DOE Human Genome Program

    Energy Technology Data Exchange (ETDEWEB)

    1992-04-01

    This report is taken from the April 1992 draft of the DOE Human Genome 1991--1992 Program Report, which is expected to be published in May 1992. The primer is intended to be an introduction to basic principles of molecular genetics pertaining to the genome project. The material contained herein is not final and may be incomplete. Techniques of genetic mapping and DNA sequencing are described.

  10. Oligocone trichromacy: clinical and molecular genetic investigations

    DEFF Research Database (Denmark)

    Andersen, Mette K G; Christoffersen, Nynne L B; Sander, Birgit

    2010-01-01

    ERG). Five patients also underwent multifocal (mf)ERG, autofluorescence recording, and optical coherence tomography (OCT). Genetic analysis included sequencing of all coding regions and flanking introns of CNGA3, CNGB3, GNAT2, KCNV2, and PDE6C. RESULTS: All patients had subnormal visual acuity, a history...... of congenital nystagmus, and subjectively normal or near-normal color vision; five patients reported photophobia. Clinical examinations revealed largely normal fundi, normal Goldmann visual field results with the IV/4e target, and normal color discrimination or mild color vision deficiency. Electrophysiological...

  11. Molecular genetics of human obesity: A comprehensive review.

    Science.gov (United States)

    Singh, Rajan Kumar; Kumar, Permendra; Mahalingam, Kulandaivelu

    2017-02-01

    Obesity and its related health complications is a major problem worldwide. Hypothalamus and their signalling molecules play a critical role in the intervening and coordination with energy balance and homeostasis. Genetic factors play a crucial role in determining an individual's predisposition to the weight gain and being obese. In the past few years, several genetic variants were identified as monogenic forms of human obesity having success over common polygenic forms. In the context of molecular genetics, genome-wide association studies (GWAS) approach and their findings signified a number of genetic variants predisposing to obesity. However, the last couple of years, it has also been noticed that alterations in the environmental and epigenetic factors are one of the key causes of obesity. Hence, this review might be helpful in the current scenario of molecular genetics of human obesity, obesity-related health complications (ORHC), and energy homeostasis. Future work based on the clinical discoveries may play a role in the molecular dissection of genetic approaches to find more obesity-susceptible gene loci. Copyright © 2016 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.

  12. Molecular genetics of pituitary development in zebrafish.

    Science.gov (United States)

    Pogoda, Hans-Martin; Hammerschmidt, Matthias

    2007-08-01

    The pituitary gland of vertebrates consists of two major parts, the neurohypophysis (NH) and the adenohypophysis (AH). As a central part of the hypothalamo-hypophyseal system (HHS), it constitutes a functional link between the nervous and the endocrine system to regulate basic body functions, such as growth, metabolism and reproduction. The development of the AH has been intensively studied in mouse, serving as a model for organogenesis and differential cell specification. However, given that the AH is a relatively recent evolutionary advance of the chordate phylum, it is also interesting to understand its development in lower chordate systems. In recent years, the zebrafish has emerged as a powerful lower vertebrate system for developmental studies, being amenable for large-scale genetic approaches, embryological manipulations, and in vivo imaging. Here, we present an overview of current knowledge of the mechanisms and genetic control of pituitary formation during zebrafish development. First, we describe the components of the zebrafish HHS, and the different pituitary cell types and hormones, followed by a description of the different steps of normal pituitary development. The central part of the review deals with the genes found to be essential for zebrafish AH development, accompanied by a description of the corresponding mutant phenotypes. Finally, we discuss future directions, with particular focus on evolutionary aspects, and some novel functional aspects with growing medical and social relevance.

  13. Molecular genetics and epigenetics of CACTA elements

    KAUST Repository

    Fedoroff, Nina V.

    2013-08-21

    The CACTA transposons, so named for a highly conserved motif at element ends, comprise one of the most abundant superfamilies of Class 2 (cut-and-paste) plant transposons. CACTA transposons characteristically include subterminal sequences of several hundred nucleotides containing closely spaced direct and inverted repeats of a short, conserved sequence of 14-15 bp. The Supressor-mutator (Spm) transposon, identified and subjected to detailed genetic analysis by Barbara McClintock, remains the paradigmatic element of the CACTA family. The Spm transposon encodes two proteins required for transposition, the transposase (TnpD) and a regulatory protein (TnpA) that binds to the subterminal repeats. Spm expression is subject to both genetic and epigenetic regulation. The Spm-encoded TnpA serves as an activator of the epigenetically inactivated, methylated Spm, stimulating both transient and heritable activation of the transposon. TnpA also serves as a negative regulator of the demethylated active element promoter and is required, in addition to the TnpD, for transposition. © Springer Science+Business Media, New York 2013.

  14. MAJOR MOLECULAR GENETIC DRIVERS IN SPORADIC PRIMARY HYPERPARATHYROIDISM.

    Science.gov (United States)

    Arnold, Andrew

    2016-01-01

    Primary hyperparathyroidism is primarily due to a solitary parathyroid adenoma but multi-gland disease, parathyroid carcinoma, and ectopic parathyroid hormone production can occur. Although primary hyperparathyroidism mostly presents sporadically, strong familial predispositions also exist. Much is known about heritable genetic mutations responsible for these syndromes, including multiple endocrine neoplasia types 1 and 2A, hyperparathyroidism-jaw tumor syndrome, and familial hypocalciuric hypercalcemia. Acquired mutations in common sporadic hyperparathyroidism have also been discovered. Here we focus on the most common and well-established genetic drivers: 1) involvement of the oncogene cyclin D1 in human neoplasia was first established in parathyroid adenomas, followed by recognition of its importance in other tumor types including breast cancer and B-lymphoid malignancy; and 2) somatic mutation of the MEN1 gene, first identified as the source of pathogenic germline mutations in patients with familial endocrinopathies, is found in a substantial fraction of non-familial parathyroid adenomas.

  15. Molecular and genetic epidemiology of cancer in low- and medium-income countries.

    Science.gov (United States)

    Malhotra, Jyoti

    2014-01-01

    Genetic and molecular factors can play an important role in an individual's cancer susceptibility and response to carcinogen exposure. Cancer susceptibility and response to carcinogen exposure can be either through inheritance of high penetrance but rare germline mutations that constitute heritable cancer syndromes, or it can be inherited as common genetic variations or polymorphisms that are associated with low to moderate risk for development of cancer. These polymorphisms can interact with environmental exposures and can influence an individual's cancer risk through multiple pathways, including affecting the rate of metabolism of carcinogens or the immune response to these toxins. Thus, these genetic polymorphisms can account for some of the geographical differences seen in cancer prevalence between different populations. This review explores the role of molecular epidemiology in the field of cancer prevention and control in low- and medium-income countries. Using data from Human Genome Project and HapMap Project, genome-wide association studies have been able to identify multiple susceptibility loci for different cancers. The field of genetic and molecular epidemiology has been further revolutionized by the discovery of newer, faster, and more efficient DNA-sequencing technologies including next-generation sequencing. The new DNA-sequencing technologies can play an important role in planning and implementation of cancer prevention and screening strategies. More research is needed in this area, especially in investigating new biomarkers and measuring gene-environment interactions. Copyright © 2014 Icahn School of Medicine at Mount Sinai. Published by Elsevier Inc. All rights reserved.

  16. Molecular and cytogenetic characterization of del(9p) syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Micale, M.A.; Haren, J.M.; Schwartz, S. [Case Western Reserve Univ. School of Medicine, Cleveland, OH (United States)] [and others

    1994-09-01

    The del(9p) syndrome is characterized by mental retardation, trigonocephaly, midface hypoplasia, upward slanting palpebral fissures, a long philtrum, and is typically associated with a breakpoint at 9p22. Seventeen unrelated patients with del(9p) and their parents were analyzed by high resolution chromosome studies, molecular analysis using a series of highly polymorphic dinucleotide repeat markers for 9p, and fluorescence in situ hybridization (FISH) to characterize precisely the extent of chromosome loss. Eleven patients were found to have an interstitial deletion with breakpoints assigned to 9p22.1 and 9p24.3 in most cases. Two patients had familial unbalanced translocations of maternal origin and four had de novo complex rearrangements identified by high resolution analysis and FISH utilizing chromosome libraries. PCR analysis of eleven families with eight minisatellite markers determined paternal origin of the deletion in six cases and maternal origin in five. This suggests that the molecular event resulting in the deletion is equally prevalent in both male and female gametogenesis and that genomic imprinting does not play a role in the pathogenesis of del(9p) syndrome. Increased precision in mapping these minisatellite markers was also possible through this work. This study demonstrates the existence of molecular heterogeneity as six patients with a cytological breakpoint at 9p22.1 revealed three different molecular breakpoints. These findings suggest that genotype-phenotype correlations in deletion syndromes such as this should be based on high-resolution molecular analysis of the deleted chromosome segment. Work is in progress to map a series of cosmid probes by FISH relative to chromosomal breakpoints in these patients. These combined studies should provide a better understanding of the mechanisms involved in the pathogenesis of del(9p) syndrome and may identify loci where genes responsible for one or more aspects of the del(9p) phenotype may reside.

  17. Genetic Breeding and Diversity of the Genus Passiflora: Progress and Perspectives in Molecular and Genetic Studies

    Directory of Open Access Journals (Sweden)

    Carlos Bernard M. Cerqueira-Silva

    2014-08-01

    Full Text Available Despite the ecological and economic importance of passion fruit (Passiflora spp., molecular markers have only recently been utilized in genetic studies of this genus. In addition, both basic genetic researches related to population studies and pre-breeding programs of passion fruit remain scarce for most Passiflora species. Considering the number of Passiflora species and the increasing use of these species as a resource for ornamental, medicinal, and food purposes, the aims of this review are the following: (i to present the current condition of the passion fruit crop; (ii to quantify the applications and effects of using molecular markers in studies of Passiflora; (iii to present the contributions of genetic engineering for passion fruit culture; and (iv to discuss the progress and perspectives of this research. Thus, the present review aims to summarize and discuss the relationship between historical and current progress on the culture, breeding, and molecular genetics of passion fruit.

  18. Molecular and genetic inflammation networks in major human diseases.

    Science.gov (United States)

    Zhao, Yongzhong; Forst, Christian V; Sayegh, Camil E; Wang, I-Ming; Yang, Xia; Zhang, Bin

    2016-07-19

    It has been well-recognized that inflammation alongside tissue repair and damage maintaining tissue homeostasis determines the initiation and progression of complex diseases. Albeit with the accomplishment of having captured the most critical inflammation-involved molecules, genetic susceptibilities, epigenetic factors, and environmental factors, our schemata on the role of inflammation in complex diseases remain largely patchy, in part due to the success of reductionism in terms of research methodology per se. Omics data alongside the advances in data integration technologies have enabled reconstruction of molecular and genetic inflammation networks which shed light on the underlying pathophysiology of complex diseases or clinical conditions. Given the proven beneficial role of anti-inflammation in coronary heart disease as well as other complex diseases and immunotherapy as a revolutionary transition in oncology, it becomes timely to review our current understanding of the molecular and genetic inflammation networks underlying major human diseases. In this review, we first briefly discuss the complexity of infectious diseases and then highlight recently uncovered molecular and genetic inflammation networks in other major human diseases including obesity, type II diabetes, coronary heart disease, late onset Alzheimer's disease, Parkinson's disease, and sporadic cancer. The commonality and specificity of these molecular networks are addressed in the context of genetics based on genome-wide association study (GWAS). The double-sword role of inflammation, such as how the aberrant type 1 and/or type 2 immunity leads to chronic and severe clinical conditions, remains open in terms of the inflammasome and the core inflammatome network features. Increasingly available large Omics and clinical data in tandem with systems biology approaches have offered an exciting yet challenging opportunity toward reconstruction of more comprehensive and dynamic molecular and genetic

  19. Unraveling molecular pathways shared by Kabuki and Kabuki-like syndromes.

    Science.gov (United States)

    Lintas, C; Persico, A M

    2017-01-31

    Kabuki syndrome (KS) is a rare genetic syndrome characterized by a typical facial gestalt, variable degrees of intellectual disability, organ malformations, postnatal growth retardation and skeletal abnormalities. So far, KMT2D or KDM6A mutation has been identified as the main cause of KS, accounting for 56%-75% and 3%-8% of cases, respectively. Patients without mutations in 1 of the 2 causative KS genes are often referred to as affected by Kabuki-like syndrome. Overall, they represent approximately 30% of KS cases, pointing toward substantial genetic heterogeneity for this condition. Here, we review all currently available literature describing KS-like phenotypes (or phenocopies) associated with genetic variants located in loci different from KMT2D and KDM6A . We also report on a new KS phenocopy harboring a 5 Mb de novo deletion in chr10p11.22-11.21. An enrichment analysis aimed at identifying functional Gene Ontology classes shared by the 2 known KS causative genes and by new candidate genes currently associated with KS-like phenotypes primarily converges upon abnormal chromatin remodeling and transcriptional dysregulation as pivotal to the pathophysiology of KS phenotypic hallmarks. The identification of mutations in genes belonging to the same functional pathways of KMT2D and KDM6A can help design molecular screenings targeted to KS-like phenotypes. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Classical and molecular genetics of the model legume Lotus japonicus.

    Science.gov (United States)

    Jiang, Q; Gresshoff, P M

    1997-01-01

    The model legume Lotus japonicus was demonstrated to be amenable to classical and molecular genetic analysis, providing the basis for the genetic dissection of the plant processes underlying nodulation and nitrogen fixation. We have developed an efficient method for the sexual hybridization of L. japonicus and obtained F1 progeny derived from a cross of L. japonicus B-129-S9 Gifu x B-581 Funakura. Over half of the cross-pollinations resulted in fertile hybrid seed, which were confirmed morphologically and by single arbitrary primer DNA amplification polymorphisms using the DAF technique. Molecular and morphological markers segregated in true Mendelian fashion in a F2 population of 100 plants. Several DAF loci were linked using the MAPMAKER software to create the first molecular linkage groups of this model legume. The mapping population was advanced to generate a set of immortal recombinant inbred lines (F6; RILs), useful for sharing plant material fixed genetically at most genomic regions. Morphological loci for waved stem shape (Ssh), dark leaf color (Lco), and short flowering period (Fpe) were inherited as single dominant Mendelian loci. DAF markers were dominant and were detected between Gifu and Funakura at about one per primer, suggesting that the parents are closely related. One polymorphism (270G generated by single octomer primer 8.6m) was linked to a morphological locus controlling leaf coloration. The results demonstrate that (i) Lotus japonicus is amenable to diploid genetic analysis, (ii) morphological and molecular markers segregate in true diploid fashion, (iii) molecular polymorphisms can be obtained at a reasonable frequency between the related Gifu and Funakura lines, and iv) the possibility exists for map-based cloning, marker assisted selection and mapping of symbiotic mutations through a genetic and molecular map.

  1. Adrenogenital syndrome: molecular mechanisms of development

    Directory of Open Access Journals (Sweden)

    V.P. Pishak

    2017-03-01

    Full Text Available On the long multistage pathway of biosynthesis of steroid hormones from cholesterol to cortisol, testo­sterone and estradiol, due to mutations in genes, there is the deficiency of steroidogenesis enzymes in the adrenal glands: cholesterol desmolase, 3β-hydroxysteroid dehydrogenase, 17α-hydroxylase, 21-hydroxylase, and enzymes of steroidogenesis in the testis: 17,20-desmolasis, 17β-hydroxystyrol dehydroreductase and others, as well as a complex of widespread congenital diseases of heterogeneous group with autosomal recessive type of inheritance — adrenogenital syndrome (AGS. Deficiency of any of these enzymes or transport proteins leads to partial or complete loss of their activity. Phenotypic manifestations of AGS are quite polymorphic: phenomenon of hypoadrenocorticism; violation of the nature and rates of sexual development; bilateral increasing of adrenal glands; hypercorticotropinemia sensitive to dexamethasone; oligo- or amenorrhea; anovulatory infertility, miscarriage in early pregnancy. Pathogenetic component of these signs is congenital disorder of steroidogenesis caused by 11β-hydroxylase deficiency and symptoms of androgen excess. In AGS, there are distinguished a phenotype and nonclassical forms of steroidogenesis enzyme deficiency. In most cases, both types of diseases occur in persons of both sexes with different course — from mild to severe forms of the disease.

  2. Molecular Models of Genetic and Organismic Structures

    CERN Document Server

    Baianu, I C

    2004-01-01

    In recent studies we showed that the earlier relational theories of organismic sets (Rashevsky,1967), Metabolic-Replication (M,R)-systems (Rosen,1958)and molecular sets (Bartholomay,1968) share a joint foundation that can be studied within a unified categorical framework of functional organismic structures (Baianu,1980. This is possible because all relational theories have a biomolecular basis, that is, complex structures such as genomes, cells,organs and biological organisms are mathematically represented in terms of biomolecular properties and entities,(that are often implicit in their representation axioms. The definition of organismic sets, for example, requires that certain essential quantities be determined from experiment: these are specified by special sets of values of general observables that are derived from physicochemical measurements(Baianu,1970; Baianu,1980; Baianu et al, 2004a.)Such observables are context-dependent and lead directly to natural transformations in categories and Topoi, that are...

  3. Progress in Genetic Studies of Tourette’s Syndrome

    Directory of Open Access Journals (Sweden)

    Yanjie Qi

    2017-10-01

    Full Text Available Tourette’s Syndrome (TS is a complex disorder characterized by repetitive, sudden, and involuntary movements or vocalizations, called tics. Tics usually appear in childhood, and their severity varies over time. In addition to frequent tics, people with TS are at risk for associated problems including attention deficit hyperactivity disorder (ADHD, obsessive-compulsive disorder (OCD, anxiety, depression, and problems with sleep. TS occurs in most populations and ethnic groups worldwide, and it is more common in males than in females. Previous family and twin studies have shown that the majority of cases of TS are inherited. TS was previously thought to have an autosomal dominant pattern of inheritance. However, several decades of research have shown that this is unlikely the case. Instead TS most likely results from a variety of genetic and environmental factors, not changes in a single gene. In the past decade, there has been a rapid development of innovative genetic technologies and methodologies, as well as significant progresses in genetic studies of psychiatric disorders. In this review, we will briefly summarize previous genetic epidemiological studies of TS and related disorders. We will also review previous genetic studies based on genome-wide linkage analyses and candidate gene association studies to comment on problems of previous methodological and strategic issues. Our main purpose for this review will be to summarize the new genetic discoveries of TS based on novel genetic methods and strategies, such as genome-wide association studies (GWASs, whole exome sequencing (WES and whole genome sequencing (WGS. We will also compare the new genetic discoveries of TS with other major psychiatric disorders in order to understand the current status of TS genetics and its relationship with other psychiatric disorders.

  4. Genomics, molecular genetics and the food industry.

    Science.gov (United States)

    Pridmore, R D; Crouzillat, D; Walker, C; Foley, S; Zink, R; Zwahlen, M C; Brüssow, H; Pétiard, V; Mollet, B

    2000-03-31

    The production of foods for an increasingly informed and selective consumer requires the coordinated activities of the various branches of the food chain in order to provide convenient, wholesome, tasty, safe and affordable foods. Also, the size and complexity of the food sector ensures that no single player can control a single process from seed production, through farming and processing to a final product marketed in a retail outlet. Furthermore, the scientific advances in genome research and their exploitation via biotechnology is leading to a technology driven revolution that will have advantages for the consumer and food industry alike. The segment of food processing aids, namely industrial enzymes which have been enhanced by the use of biotechnology, has proven invaluable in the production of enzymes with greater purity and flexibility while ensuring a sustainable and cheap supply. Such enzymes produced in safe GRAS microorganisms are available today and are being used in the production of foods. A second rapidly evolving segment that is already having an impact on our foods may be found in the new genetically modified crops. While the most notorious examples today were developed by the seed companies for the agro-industry directed at the farming sector for cost saving production of the main agronomical products like soya and maize, its benefits are also being seen in the reduced use of herbicides and pesticides which will have long term benefits for the environment. Technology-driven advances for the food processing industry and the consumer are being developed and may be divided into two separate sectors that will be presented in greater detail: 1. The application of genome research and biotechnology to the breeding and development of improved plants. This may be as an aid for the cataloging of industrially important plant varieties, the rapid identification of key quality traits for enhanced classical breeding programs, or the genetic modification of

  5. [Algorithm for the molecular analysis of Bardet-Biedl syndrome in Spain].

    Science.gov (United States)

    Castro-Sánchez, Sheila; Álvarez-Satta, María; Pereiro, Inés; Piñeiro-Gallego, M Teresa; Valverde, Diana

    2015-08-21

    Bardet-Biedl syndrome (BBS) is a multisystemic genetic disorder, which is not widespread among the Caucasian population, characterized by a highly variable phenotype and great genetic heterogeneity. BBS belongs to a group of diseases called ciliopathies, caused by defects in the structure and/or function of cilia. Due to the diagnostic complexity of the syndrome, the objective of this study was to analyse our whole group of patients in order to create an algorithm to facilitate the routine molecular diagnosis of BBS. We also calculated several epidemiological parameters in our cohort. We analysed 116 BBS patients belonging to 89 families from the whole Spanish geography. All probands fulfilled diagnosis criteria established for BBS. For this, we used: genotyping microarray, direct sequencing and homozygosis mapping (in consanguineous families). By means of the different approaches, it was possible to diagnose 47% of families (21% by genotyping microarray, 18% by direct sequencing of predominant BBS genes, and 8% by homozygosis mapping). With regard to epidemiological data, a prevalence value of 1:407,000 was obtained for BBS in Spain, and a sex ratio of 1.4:1 (men:women). The proposed algorithm, based on the analysis of predominant BBS genes combined with homozygosis mapping, allowed us to confirm the molecular diagnosis in a significant percentage of families with clinically suspected BBS. This diagnostic algorithm will be useful for the improvement of the efficiency of molecular analysis in BBS. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  6. Molecular and genetic study of wheat rusts | Le Maitre | African ...

    African Journals Online (AJOL)

    Molecular and genetic study of wheat rusts. ... Puccinia triticina, Puccinia graminis and Puccinia striiformis cause leaf, stem and yellow rust, respectively. Wheat rusts can cause ... Breeding resistant cultivars is a long process and requires an accurate picture of the current and future pathogen population. Differentiation of ...

  7. [Molecular genetic investigation of sugar beet (Beta vulgaris L.)].

    Science.gov (United States)

    Butorina, A K; Kornienko, A V

    2011-10-01

    Molecular genetic studies of sugar beet (Beta vulgaris L.) are reviewed as a basis for the development of genomics of this species. The methods used to study structural and functional genomics are considered. The results and their application to increase the efficiency of sugar beet breeding are discussed.

  8. Use of molecular genetics and historical records to reconstruct the ...

    African Journals Online (AJOL)

    GRACE

    2006-12-29

    Dec 29, 2006 ... analysis of gene pools from modern populations possible. The technology uses genetic markers to ... The use of these molecular techniques together with historical records in an integrated manner can greatly benefit the .... This approach maximizes cost- and time effectiveness with information deriving from ...

  9. Molecular Genetics and Hormones: New Frontiers in Entrepreneurship Research

    NARCIS (Netherlands)

    M.J.H.M. van der Loos (Matthijs)

    2013-01-01

    textabstractRecent studies suggest that entrepreneurship is partly heritable, but are unable to pinpoint the specific genes involved. This thesis presents results from novel research aiming to identify genes associated with entrepreneurship using genetic data on the molecular level. In addition, the

  10. Recent developments in the molecular genetic understanding of breast cancer

    NARCIS (Netherlands)

    Devilee, P.; Schuuring, E.; van de Vijver, M. J.; Cornelisse, C. J.

    1994-01-01

    The molecular genetic characterization of breast cancer has implicated or identified the involvement of at least 10 distinct gene alterations in the genesis or progression of this disease. The genes involved fall into three distinct classes, possibly reflecting their particular function in the

  11. Molecular markers for genetic diversity and phylogeny research of ...

    African Journals Online (AJOL)

    Brazilian sheep descended from several breeds brought to the New World by Portuguese and Spanish colonists, and they have evolved and adapted to local climatic variations and acquired tolerance or resistance to many diseases. Molecular markers are widely used in analyzing genetic variability, and markers such as ...

  12. The molecular basis of South African genetic porphyria established ...

    African Journals Online (AJOL)

    genetic drift (the operation of chance factors resulting in the high (or low) frequency of a gene in a population) .... island continent. He claims that some present-day descendants of those men suffer from VP. If molecular studies were to show that they have one of the Afrikaner mutations, this would be good indirect evidence ...

  13. Population and molecular genetics of root-knot nematodes

    NARCIS (Netherlands)

    Dautova, M.

    2001-01-01

    This thesis describes studies of root-knot nematodes Meloidogyne spp. - an economically important pest in agriculture - using population and molecular genetics. Variability in virulence to Mi bearing tomato genotypes is shown for

  14. Molecular genetic study of hemophilia B in an Algerian population

    African Journals Online (AJOL)

    DELL

    2016-12-21

    Dec 21, 2016 ... genetic predisposition of developing inhibitors. The objective of this study were, to identify the mutations that produce different forms of HB disease among Algerian patients, to characterise mutations of the. FIX gene and to develop our knowledge about the molecular basis of this disease. MATERIALS AND ...

  15. Isolation and molecular genetic characterization of a yeast strain ...

    African Journals Online (AJOL)

    The yeast was identified by molecular genetics technique based on sequence analysis of the variable D1/D2 domain of the large subunit (26S) ribosomal DNA. Subsequent 26S rRNA gene sequencing showed 100% base sequence homology and it was identified as Candida viswanathii. The degradation of PAHs

  16. Molecular analysis of genetic diversity in elite II synthetic hexaploid ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-07-20

    Jul 20, 2009 ... Full Length Research Paper. Molecular analysis of genetic diversity in elite II synthetic hexaploid wheat screened against Barley yellow dwarf virus. Huma Saffdar1 ... The history of cultiva- ted wheat and human .... and viewed under the UV light chamber using the computer pro- gram UVIPhotoMW.

  17. The molecular genetics of crown gall tumorigenesis

    International Nuclear Information System (INIS)

    Hooykaas, P.J.J.; Schilperoort, R.A.

    1984-01-01

    The phytopathogenic bacteria Agrobacterium tumefaciens and A. rhizogenes are the causative agents of the widespread plant diseases ''crown gall'' and ''hairy root'' respectively. It is now well established that virulent strains of these bacterial species transfer a piece of bacterial DNA into plant cells, thereby transforming these into tumor cells. In research much attention has been paid to the agrobacteria for several reasons. First is the desire to develop a system for the genetic engineering of plant cells based on the natural system for gene transfer between Agrobacterium species and plant cells. Second, there is a striking resemblance between the etiology of animal cancers and the plant cancer crown gall that was recognized as early as in 1927. This led to basic studies on the process of plant tumor induction and on the recovery of plant cells from the tumorous state. A third important interest lies in crown gall as a disease that is the cause of economically important losses in agriculture an horticulture in Europe, North America, and Austrailia. Research has been aimed at finding means to prevent crown gall and to cure plants of this disease

  18. Clinical and genetic aspects of Marfan syndrome and familial thoracic aortic aneurysms and dissections

    NARCIS (Netherlands)

    Hilhorst-Hofstee, Yvonne

    2013-01-01

    This thesis concerns the clinical and genetic aspects of familial thoracic aortic aneurysms and dissections, in particular in Marfan syndrome. It includes the Dutch multidisciplinary guidelines for diagnosis and management of Marfan syndrome. These guidelines contain practical directions for

  19. Molecular genetic markers of breast cancer

    Directory of Open Access Journals (Sweden)

    K. A. Grishina

    2016-01-01

    Full Text Available Breast cancer (BC is the second most common type of cancer worldwide and affects 1 in 8 women over the course of their lifetime. A personalized approach to treating BC can substantially increase efficiency and consequently maintain the active life of many people. This encourages investigators and physicians to better understand tumor biology in order to make a correct diagnosis, to determine recurrence risk, and to choose adequate therapy. This paper discusses the bases for the molecular classification of BC into its expression subtypes, as well as current prognostic kits that assist oncologists in classifying the subtypes of cancer and in predicting the development of the disease. The existing test systems are not universal, each of them is applicable only to a limited group of patients, but they totally cover a considerable number of cases. The tumor gene mutations in BC, which have been characterized by up-to-date methods, can serve as predictive markers for the efficiency of targeted therapy.

  20. Molecular genetic studies on irradiated wheat plants

    International Nuclear Information System (INIS)

    Saleh, O.M.

    2002-01-01

    Composite genotype(octamer hybrid) was obtained from crossing among eight Egyptian hexaploid wheat cultivars differing in their tolerance to drought stress to produce a genotype, which can economize on the irrigation water requirements or can tolerate drought stress. Gamma irradiation with 10-Krad was used to induce mutations, which could improve drought tolerance for this composite. From eight Egyptian wheat cultivars, two were chosen as drought tolerant and drought sensitive genotypes (G-160 and Sk-61, respectively. They were evaluated along with their F1 and F2 for their relative drought tolerance for some yield-related traits. Bulked segregating analysis developed some RAPD and SSR markers with different primers, which were considered as molecular for drought tolerance in wheat. Hal 2-like gene was introduced into Egyptian wheat cultivar G-164 via micro projectile bombardment. Two putative transgenic plants were successfully detected by leaf painting with the herbicide basta. PCR/ Southern blotting analysis indicated the presence of both/either bar and/or Hal 2-like genes in the genomic background of the two transgenic plants

  1. Intelligent DNA-based molecular diagnostics using linked genetic markers

    Energy Technology Data Exchange (ETDEWEB)

    Pathak, D.K.; Perlin, M.W.; Hoffman, E.P.

    1994-12-31

    This paper describes a knowledge-based system for molecular diagnostics, and its application to fully automated diagnosis of X-linked genetic disorders. Molecular diagnostic information is used in clinical practice for determining genetic risks, such as carrier determination and prenatal diagnosis. Initially, blood samples are obtained from related individuals, and PCR amplification is performed. Linkage-based molecular diagnosis then entails three data analysis steps. First, for every individual, the alleles (i.e., DNA composition) are determined at specified chromosomal locations. Second, the flow of genetic material among the individuals is established. Third, the probability that a given individual is either a carrier of the disease or affected by the disease is determined. The current practice is to perform each of these three steps manually, which is costly, time consuming, labor-intensive, and error-prone. As such, the knowledge-intensive data analysis and interpretation supersede the actual experimentation effort as the major bottleneck in molecular diagnostics. By examining the human problem solving for the task, we have designed and implemented a prototype knowledge-based system capable of fully automating linkage-based molecular diagnostics in X-linked genetic disorders, including Duchenne Muscular Dystrophy (DMD). Our system uses knowledge-based interpretation of gel electrophoresis images to determine individual DNA marker labels, a constraint satisfaction search for consistent genetic flow among individuals, and a blackboard-style problem solver for risk assessment. We describe the system`s successful diagnosis of DMD carrier and affected individuals from raw clinical data.

  2. MOLECULAR-GENETIC «PORTRAIT» OF BREAST CANCER

    Directory of Open Access Journals (Sweden)

    S. A. Laptiev

    2017-01-01

    Full Text Available Understanding genetic mechanisms and detection of biological markers of tumor growth forms an individual molecular phenotype oftransformed cells that characterizes stage of tumor, the ability to metastasize, hormonal sensitivity, chemotherapyefficiencyetc. Mutations in proto- and anti-oncogenes controlling mitotic activity of cells and their ability to DNA reparation are often found in tumor cells in patients with cancer. Defects of classical tumor suppressor genes (BRCA1/2, CHEK2, ATM, PALB2, NBS1, TP53, etc. determine the hereditary predisposition to breast cancer caused by genomic instability and appearance of «chimeric» genes, aneuploidies and chromosomal aberrations. Breast cancer is a genetically heterogeneous disease with various molecular, biological and clinical features. Identificationof the molecular phenotype of breast carcinomas is an important prognostic factor of the disease, and it helps to individualize the therapeutic approach for patients.

  3. Uncommon genetic syndromes and narrative production - Case Studies with Williams, Smith-Magenis and Prader- Willi Syndromes

    OpenAIRE

    Garayzábal Heinze, Elena; Capo, Magdalena; Moruno Lopéz, Esther; Gonçalves, Óscar F.; Férnandez, Montserrat; Lens, María; Sampaio, Adriana

    2012-01-01

    This study compares narrative production among three syndromes with genetic microdeletions: Williams syndrome (WS), Smith-Magenis syndrome (SMS), and Prader-Willi syndrome (PWS), characterized by intellectual disabilities and relatively spared language abilities. Our objective is to study the quality of narrative production in the context of a common intellectual disability. To elicit a narrative production, the task Frog! Where Are You was used. Then, structure, process, an...

  4. Corn Storage Protein - A Molecular Genetic Model

    Energy Technology Data Exchange (ETDEWEB)

    Messing, Joachim [Rutgers Univ., Piscataway, NJ (United States)

    2013-05-31

    Corn is the highest yielding crop on earth and probably the most valuable agricultural product of the United States. Because it converts sun energy through photosynthesis into starch and proteins, we addressed energy savings by focusing on protein quality. People and animals require essential amino acids derived from the digestion of proteins. If proteins are relatively low in certain essential amino acids, the crop becomes nutritionally defective and has to be supplemented. Such deficiency affects meat and fish production and countries where corn is a staple. Because corn seed proteins have relatively low levels of lysine and methionine, a diet has to be supplemented with soybeans for the missing lysine and with chemically synthesized methionine. We therefore have studied genes expressed during maize seed development and their chromosomal organization. A critical technical requirement for the understanding of the molecular structure of genes and their positional information was DNA sequencing. Because of the length of sequences, DNA sequencing methods themselves were insufficient for this type of analysis. We therefore developed the so-called “DNA shotgun sequencing” strategy, where overlapping DNA fragments were sequenced in parallel and used to reconstruct large DNA molecules via overlaps. Our publications became the most frequently cited ones during the decade of 1981-1990 and former Associate Director of Science for the Office of Basic Energy Sciences Patricia M. Dehmer presented our work as one of the great successes of this program. A major component of the sequencing strategy was the development of bacterial strains and vectors, which were also used to develop the first biotechnology crops. These crops possessed new traits thanks to the expression of foreign genes in plants. To enable such expression, chimeric genes had to be constructed using our materials and methods by the industry. Because we made our materials and methods freely available to

  5. Genetic predisposition increases the tic severity, rate of comorbidities, and psychosocial and educational difficulties in children with Tourette syndrome.

    Science.gov (United States)

    Eysturoy, Absalon Niclas; Skov, Liselotte; Debes, Nanette Mol

    2015-03-01

    This study aimed to examine whether there are differences in tic severity, comorbidities, and psychosocial and educational consequences in children with Tourette syndrome and genetic predisposition to Tourette syndrome compared with children with Tourette syndrome without genetic predisposition to Tourette syndrome. A total of 314 children diagnosed with Tourette syndrome participated in this study. Validated diagnostic tools were used to assess tic severity, comorbidities, and cognitive performance. A structured interview was used to evaluate psychosocial and educational consequences related to Tourette syndrome. The children with Tourette syndrome and genetic predisposition present with statistically significant differences in terms of severity of tics, comorbidities, and a range of psychosocial and educational factors compared with the children with Tourette syndrome without genetic predisposition. Professionals need to be aware of genetic predisposition to Tourette syndrome, as children with Tourette syndrome and genetic predisposition have more severe symptoms than those children with Tourette syndrome who are without genetic predisposition. © The Author(s) 2014.

  6. Genetic aspects of the antiphospholipid syndrome: An update.

    Science.gov (United States)

    Sebastiani, Gian Domenico; Iuliano, Annamaria; Cantarini, Luca; Galeazzi, Mauro

    2016-05-01

    Studies on the immunogenetic predisposition to antiphospholipid syndrome (APS) and on other non-genetic and epigenetic factors are summarised and discussed. Family studies suggest a genetic predisposition to APS. It appears that this genetic predisposition is in part accounted for by the HLA system, the most consistent associations being those with DR4 and DRw53. Furthermore, it appears that lupus anticoagulant (LA) and anticardiolipin (aCL) antibodies are both associated with the same HLA antigens. Population studies suggest that HLA genes have a role in conferring susceptibility to develop primary APS, with some differences in different ethnic groups. Other genes, outside the MHC, give their contribution to the development of this autoimmune syndrome, such as IRF5, STAT4 and those related to inherited thrombophilia--factor V Leiden and G20210A prothrombin polymorphisms. Finally, post-transcriptional modifications of anti-beta2GPI antibodies could be implicated too. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Molecular genetics of autism spectrum disorder

    Directory of Open Access Journals (Sweden)

    Luciana Fariña

    2015-11-01

    Full Text Available Los Trastornos del Espectro Autista son un grupo de trastornos neuropsiquiátricos heterogéneos tanto en su fenotipo como en su etiología. La importancia del tema radica en el aumento de la prevalencia, siendo actualmente la prevalencia mundial de 60 a 90 casos cada 10.000 personas. En Uruguay no se cuenta con datos epidemiológicos sobre estos y otros trastornos del desarrollo pero se estima aproximadamente entre 6 a 7 casos cada 1000 personas. El siguiente trabajo monográfico intenta actualizar sobre la etiología, diagnóstico y aplicaciones de la genética molecular en los Trastornos del Espectro Autista con el fin de contribuir a la comprensión de los mismos, generando una posible herramienta para los profesionales de la salud. Estos trastornos son uno de los cuadros de la psiquiatría infantil con mayor impacto familiar y es de destacar la importancia del componente genético en su etiología. Se ha puesto en evidencia tanto en estudios clásicos de genética como a través de las nuevas tecnologías como Genome Wide Association Studies, microarrays y secuenciación del genoma completo el rol que juega la genética en la etiología de dichos trastornos. El conocimiento de la base genética que subyace a los Trastornos del Espectro Autista posibilita la detección de casos de acuerdo a un perfil genético que ayude a encontrar grupos con fenotipos similares. Esto permitirá en un futuro desarrollar medidas de prevención, realizar diagnósticos precoces y dirigir el tratamiento de acuerdo a su base etiológica, lo que tendrá mayor impacto en el pronóstico de estos pacientes.

  8. Genetic diversity analysis of common beans based on molecular markers

    Directory of Open Access Journals (Sweden)

    Homar R. Gill-Langarica

    2011-01-01

    Full Text Available A core collection of the common bean (Phaseolus vulgaris L., representing genetic diversity in the entire Mexican holding, is kept at the INIFAP (Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias, Mexico Germplasm Bank. After evaluation, the genetic structure of this collection (200 accessions was compared with that of landraces from the states of Oaxaca, Chiapas and Veracruz (10 genotypes from each, as well as a further 10 cultivars, by means of four amplified fragment length polymorphisms (AFLP +3/+3 primer combinations and seven simple sequence repeats (SSR loci, in order to define genetic diversity, variability and mutual relationships. Data underwent cluster (UPGMA and molecular variance (AMOVA analyses. AFLP analysis produced 530 bands (88.5% polymorphic while SSR primers amplified 174 alleles, all polymorphic (8.2 alleles per locus. AFLP indicated that the highest genetic diversity was to be found in ten commercial-seed classes from two major groups of accessions from Central Mexico and Chiapas, which seems to be an important center of diversity in the south. A third group included genotypes from Nueva Granada, Mesoamerica, Jalisco and Durango races. Here, SSR analysis indicated a reduced number of shared haplotypes among accessions, whereas the highest genetic components of AMOVA variation were found within accessions. Genetic diversity observed in the common-bean core collection represents an important sample of the total Phaseolus genetic variability at the main Germplasm Bank of INIFAP. Molecular marker strategies could contribute to a better understanding of the genetic structure of the core collection as well as to its improvement and validation.

  9. Genetic rodent models of obesity-associated ovarian dysfunction and subfertility: insights into polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Isabel eHuang-Doran

    2016-06-01

    Full Text Available Polycystic ovary syndrome (PCOS is the most common endocrinopathy affecting women, and a leading cause of female infertility worldwide. Defined clinically by the presence of hyperandrogenemia and oligomenorrhoea, PCOS represents a state of hormonal dysregulation, disrupted ovarian follicle dynamics, and subsequent oligo- or anovulation. The syndrome’s prevalence is attributed at least partly to a well-established association with obesity and insulin resistance (IR. Indeed, the presence of severe PCOS in human genetic obesity and IR syndromes supports a causal role for IR in the pathogenesis of PCOS. The molecular mechanisms underlying this causality, however, as well as the important role of hyperandrogenemia, remain poorly elucidated. As such, treatment of PCOS is necessarily empirical, focusing on symptom alleviation. The generation of knockout and transgenic rodent models of obesity and IR offer a promising platform in which to address mechanistic questions about reproductive dysfunction in the context of metabolic disease. The impact of primary perturbations in rodent gonadotrophin or androgen signaling has been similarly interrogated. The insights gained from such models, however, have been limited by the relatively poor fidelity of rodent models to human PCOS. In this minireview we evaluate the ovarian phenotypes associated with rodent models of obesity and IR, including the extent of endocrine disturbance, ovarian dysmorphology and subfertility. We compare them to both human PCOS and other animal models of the syndrome (genetic and hormonal, explore reasons for their discordance and consider the new opportunities that are emerging to better understand and treat this important condition.

  10. Genetics Home Reference: hereditary angiopathy with nephropathy, aneurysms, and muscle cramps syndrome

    Science.gov (United States)

    ... potential to burst, causing bleeding within the brain ( hemorrhagic stroke ). However, in people with HANAC syndrome , these aneurysms ... Diagnostic Tests Drug Therapy Genetic Counseling Palliative Care Surgery and Rehabilitation Related Information How are genetic conditions ...

  11. Numerical Magnitude Processing Impairments in Genetic Syndromes: A Cross-Syndrome Comparison of Turner and 22Q11.2 Deletion Syndromes

    Science.gov (United States)

    Brankaer, Carmen; Ghesquière, Pol; De Wel, Anke; Swillen, Ann; De Smedt, Bert

    2017-01-01

    Cross-syndrome comparisons offer an important window onto understanding heterogeneity in mathematical learning disabilities or dyscalculia. The present study therefore investigated symbolic numerical magnitude processing in two genetic syndromes that are both characterized by mathematical learning disabilities: Turner syndrome and 22q11.2 deletion…

  12. Prader-Willi syndrome: a review of clinical, genetic, and endocrine findings.

    Science.gov (United States)

    Angulo, M A; Butler, M G; Cataletto, M E

    2015-12-01

    Prader-Willi syndrome (PWS) is a multisystemic complex genetic disorder caused by lack of expression of genes on the paternally inherited chromosome 15q11.2-q13 region. There are three main genetic subtypes in PWS: paternal 15q11-q13 deletion (65-75 % of cases), maternal uniparental disomy 15 (20-30 % of cases), and imprinting defect (1-3 %). DNA methylation analysis is the only technique that will diagnose PWS in all three molecular genetic classes and differentiate PWS from Angelman syndrome. Clinical manifestations change with age with hypotonia and a poor suck resulting in failure to thrive during infancy. As the individual ages, other features such as short stature, food seeking with excessive weight gain, developmental delay, cognitive disability and behavioral problems become evident. The phenotype is likely due to hypothalamic dysfunction, which is responsible for hyperphagia, temperature instability, high pain threshold, hypersomnia and multiple endocrine abnormalities including growth hormone and thyroid-stimulating hormone deficiencies, hypogonadism and central adrenal insufficiency. Obesity and its complications are the major causes of morbidity and mortality in PWS. An extensive review of the literature was performed and interpreted within the context of clinical practice and frequently asked questions from referring physicians and families to include the current status of the cause and diagnosis of the clinical, genetics and endocrine findings in PWS. Updated information regarding the early diagnosis and management of individuals with Prader-Willi syndrome is important for all physicians and will be helpful in anticipating and managing or modifying complications associated with this rare obesity-related disorder.

  13. Hereditary kidney cancer syndromes: Genetic disorders driven by alterations in metabolism and epigenome regulation.

    Science.gov (United States)

    Hasumi, Hisashi; Yao, Masahiro

    2018-03-01

    Although hereditary kidney cancer syndrome accounts for approximately five percent of all kidney cancers, the mechanistic insight into tumor development in these rare conditions has provided the foundation for the development of molecular targeting agents currently used for sporadic kidney cancer. In the late 1980s, the comprehensive study for hereditary kidney cancer syndrome was launched in the National Cancer Institute, USA and the first kidney cancer-associated gene, VHL, was identified through kindred analysis of von Hippel-Lindau (VHL) syndrome in 1993. Subsequent molecular studies on VHL function have elucidated that the VHL protein is a component of E3 ubiquitin ligase complex for hypoxia-inducible factor (HIF), which provided the basis for the development of tyrosine kinase inhibitors targeting the HIF-VEGF/PDGF pathway. Recent whole-exome sequencing analysis of sporadic kidney cancer exhibited the recurrent mutations in chromatin remodeling genes and the later study has revealed that several chromatin remodeling genes are altered in kidney cancer kindred at the germline level. To date, more than 10 hereditary kidney cancer syndromes together with each responsible gene have been characterized and most of the causative genes for these genetic disorders are associated with either metabolism or epigenome regulation. In this review article, we describe the molecular mechanisms of how an alteration of each kidney cancer-associated gene leads to renal tumorigenesis as well as denote therapeutic targets elicited by studies on hereditary kidney cancer. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  14. Genetic Basis of Nonsyndromic and Syndromic Tooth Agenesis

    Science.gov (United States)

    Ye, Xiaoqian; Attaie, Ali B.

    2016-01-01

    Human dentition development is a long and complex process which involves a series of reciprocal and sequential interactions between the embryonic stomodeal epithelium and the underlying neural crest–derived mesenchyme. Despite environment disturbances, tooth development is predominantly genetically controlled. To date, more than 200 genes have been identified in tooth development. These genes implied in various signaling pathways such as the bone morphogenetic protein, fibroblast growth factor, sonic hedgehog homolog, ectodysplasin A, wingless-type MMTV integration site family (Wnt), and transform growth factor pathways. Mutations in any of these strictly balanced signaling cascades may cause arrested odontogenesis and/or other dental defects. This article aims to review current knowledge about the genetic mechanisms responsible for selective nonsyndromic tooth agenesis in humans and to present a detailed summary of syndromes with hypodontia as regular features and their causative genes. PMID:27895972

  15. Genetics of Cd36 and the hypertension metabolic syndrome

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Kurtz, T. W.

    2002-01-01

    Roč. 22, č. 2 (2002), s. 148-153 ISSN 0270-9295 R&D Projects: GA ČR(CZ) GA301/00/1636; GA MŠk(CZ) LN00A079; GA ČR(CZ) GV204/98/K015 Grant - others:NIHFogarty(US) RO3TW001236 Institutional research plan: CEZ:AV0Z5011922 Keywords : Cd36 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.176, year: 2002

  16. Genetics of Cd36 and the hypertension metabolic syndrome

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Kurtz, W. T.

    2002-01-01

    Roč. 22, č. 2 (2002), s. 148-153 ISSN 0270-9295 R&D Projects: GA ČR GV204/98/K015; GA ČR GA301/00/1636; GA MŠk LN00A079 Grant - others:NIHFogarty(US) RO3TW001236 Institutional research plan: CEZ:AV0Z5011922 Keywords : Cd36 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.176, year: 2002

  17. Molecular Pathogenesis of Familial Wolff-Parkinson-White Syndrome.

    Science.gov (United States)

    Licht, Miyamotoa

    2018-01-01

    Familial Wolff-Parkinson-White (WPW) syndrome is an autosomal dominant inherited disease and consists of a small percentage of WPW syndrome which exhibits ventricular pre-excitation by development of accessory atrioventricular pathway. A series of mutations in PRKAG2 gene encoding gamma2 subunit of 5'AMP-activated protein kinase (AMPK) has been identified as the cause of familial WPW syndrome. AMPK is one of the most important metabolic regulators of carbohydrates and lipids in many types of tissues including cardiac and skeletal muscles. Patients and animals with the mutation in PRKAG2 gene exhibit aberrant atrioventricular conduction associated with cardiac glycogen overload. Recent studies have revealed "novel" significance of canonical pathways leading to glycogen synthesis and provided us profound insights into molecular mechanism of the regulation of glycogen metabolism by AMPK. This review focuses on the molecular basis of the pathogenesis of cardiac abnormality due to PRKAG2 mutation and will provide current overviews of the mechanism of glycogen regulation by AMPK. J. Med. Invest. 65:1-8, February, 2018.

  18. Inherited ichthyosis: Syndromic forms.

    Science.gov (United States)

    Yoneda, Kozo

    2016-03-01

    Among diseases that cause ichthyosis as one of the symptoms, there are some diseases that induce abnormalities in organs other than the skin. Of these, diseases with characteristic signs are regarded as syndromes. Although these syndromes are very rare, Netherton syndrome, Sjögren-Larsson syndrome, Conradi-Hünermann-Happle syndrome, Dorfman-Chanarin syndrome, ichthyosis follicularis, atrichia and photophobia (IFAP) syndrome, and Refsum syndrome have been described in texts as representative ones. It is important to know the molecular genetics and pathomechanisms in order to establish an effective therapy and beneficial genetic counseling including a prenatal diagnosis. © 2016 Japanese Dermatological Association.

  19. [Isolated and syndromic forms of oesophageal atresia - genetic aspects and counselling].

    Science.gov (United States)

    Smigiel, Robert; Karpiński, Paweł; Patkowski, Dariusz

    2009-01-01

    Oesophageal atresia is a congenital developmental defect of alimentary tract concerning the interruption of oesophagus with or without connection with the trachea. The incidence of oesophageal atresia is 1:3000-3500 of live-born infants. Associated anomalies occur in 50% of patients (syndromic cases). In the rest of the patients with oesophageal atresia these anomalies are isolated (non-syndromic cases). The knowledge of dysmorphic syndromes with oesophageal defects, allows us to diagnose the complex genetic syndromes and to implement the correct treatment and correct genetic counselling concerning the etiology, natural course of the disease, prognosis and possible complications as well as determining the recurrence risk of the disease in the family. The authors describe the chosen embryological, epidemiological and genetic aspects of congenital oesophageal atresia. The clinical aspects, genetic counselling as well as the genetic basis of chosen genetic syndromes with oesophageal atresia are also described in this article.

  20. Understanding the molecular mechanisms of human microtia via a pig model of HOXA1 syndrome

    Directory of Open Access Journals (Sweden)

    Ruimin Qiao

    2015-06-01

    Full Text Available Microtia is a congenital malformation of the outer ears. Although both genetic and environmental components have been implicated in microtia, the genetic causes of this innate disorder are poorly understood. Pigs have naturally occurring diseases comparable to those in humans, providing exceptional opportunity to dissect the molecular mechanism of human inherited diseases. Here we first demonstrated that a truncating mutation in HOXA1 causes a monogenic disorder of microtia in pigs. We further performed RNA sequencing (RNA-Seq analysis on affected and healthy pig embryos (day 14.25. We identified a list of 337 differentially expressed genes (DEGs between the normal and mutant samples, shedding light on the transcriptional network involving HOXA1. The DEGs are enriched in biological processes related to cardiovascular system and embryonic development, and neurological, renal and urological diseases. Aberrant expressions of many DEGs have been implicated in human innate deformities corresponding to microtia-associated syndromes. After applying three prioritizing algorithms, we highlighted appealing candidate genes for human microtia from the 337 DEGs. We searched for coding variants of functional significance within six candidate genes in 147 microtia-affected individuals. Of note, we identified one EVC2 non-synonymous mutation (p.Asp1174Asn as a potential disease-implicating variant for a human microtia-associated syndrome. The findings advance our understanding of the molecular mechanisms underlying human microtia, and provide an interesting example of the characterization of human disease-predisposing variants using pig models.

  1. Prenatal molecular testing for Beckwith-Wiedemann and Silver-Russell syndromes

    DEFF Research Database (Denmark)

    Eggermann, Thomas; Brioude, Frédéric; Russo, Silvia

    2016-01-01

    Beckwith-Wiedemann and Silver-Russell syndromes (BWS/SRS) are two imprinting disorders (IDs) associated with disturbances of the 11p15.5 chromosomal region. In BWS, epimutations and genomic alterations within 11p15.5 are observed in >70% of patients, whereas in SRS they are observed in about 60% ......, the consequences for prenatal genetic testing and counseling and our cumulative experience in dealing with these disorders.European Journal of Human Genetics advance online publication, 28 October 2015; doi:10.1038/ejhg.2015.224....... molecular findings underlying these disorders are a challenge not only for laboratories offering these tests but also for geneticists counseling affected families. The scope of counseling must consider the range of detectable disturbances and their origin, the lack of precise quantitative knowledge...

  2. Metabolic syndrome and Cancer: Do they share common molecular pathways?

    Directory of Open Access Journals (Sweden)

    Veniou E.

    2016-06-01

    Full Text Available Metabolic syndrome, a clustering of risk factors including obesity, has emerged as a global health plague. A lot of epidemiological and clinical evidence suggests that the metabolic syndrome is linked not only to cardiovascular diseases and diabetes mellitus type 2 but also to cancer development and progression. In this review the potential mechanisms tying the metabolic syndrome with cancer are presented. The role of insulin resistance and hyperinsulinemia, the activation of insulin-like growth factor-1 (IGF-1 pathway, and the induction of cytotoxic products are highlighted. Subsequent effects leading to oxidative stress, release of lipokines with signaling properties by adipocytes, development of a sustained systemic inflammation, production of inflammatory cytokines, and establishment of a tumorigenic environment are also discussed. The importance of the metabolic syndrome and obesity coupled with the deeper understanding of the underlying molecular mechanisms has trigger intensive clinical research with an aim to prevent the risk of cancer and improve outcomes. Moreover, the need for lifestyle changes with increased physical activity and improved dietary quality has been emerged as urgent health priority.

  3. Forensic interpretation of molecular variation on networks of disease transmission and genetic inheritance.

    Science.gov (United States)

    Velsko, Stephan P; Osburn, Joanne; Allen, Jonathan

    2014-11-01

    This paper describes the inference-on-networks (ION) framework for forensic interpretat ION of molecular typing data in cases involving allegations of infectious microbial transmission, association of disease outbreaks with alleged sources, and identifying familial relationships using mitochondrial or Y chromosomal DNA. The framework is applicable to molecular typing data obtained using any technique, including those based on electrophoretic separations. A key insight is that the networks associated with disease transmission or DNA inheritance can be used to define specific testable relationships and avoid the ambiguity and subjectivity associated with the criteria used for inferring genetic relatedness now in use. We discuss specific applications of the framework to the 2003 severe acute respiratory syndrome (SARS) outbreak in Singapore and the 2001 foot-and-mouth disease virus (FMDV) outbreak in Great Britain. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  4. Clinical and molecular phenotype of Aicardi-Goutieres syndrome

    DEFF Research Database (Denmark)

    Rice, Gillian; Patrick, Teresa; Parmar, Rekha

    2007-01-01

    Aicardi-Goutieres syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3'-->5' exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease...... identified an RNASEH2A or RNASEH2B mutation on one allele only. In one child, the disease occurred because of a de novo heterozygous TREX1 mutation. In 22 families, no mutations were found. Null mutations were common in TREX1, although a specific missense mutation was observed frequently in patients from...

  5. Antigenic variation: Molecular and genetic mechanisms of relapsing disease

    Energy Technology Data Exchange (ETDEWEB)

    Cruse, J.M.; Lewis, R.E.

    1987-01-01

    This book contains 10 chapters. They are: Contemporary Concepts of Antigenic Variation; Antigenic Variation in the Influenza Viruses; Mechanisms of Escape of Visna Lentiviruses from Immunological Control; A Review of Antigenic Variation by the Equine Infectious Anemia Virus; Biologic and Molecular Variations in AIDS Retrovirus Isolates; Rabies Virus Infection: Genetic Mutations and the Impact on Viral Pathogenicity and Immunity; Immunobiology of Relapsing Fever; Antigenic Variation in African Trypanosomes; Antigenic Variation and Antigenic Diversity in Malaria; and Mechanisms of Immune Evasion in Schistosomiasis.

  6. Genetics of the cardiometabolic syndrome: new insights and therapeutic implications.

    Science.gov (United States)

    Sookoian, Silvia; Pirola, Carlos J

    2007-10-01

    Although the definition of the phenotype is imprecise, cardiometabolic syndrome (CMS) includes a constellation of complex diseases such as type 2 diabetes, dislipidemias, central obesity and hypertension, proinflammatory and prothrombotic states, ovarian polycystosis and fatty liver. The genetics of each disease is complex in itself and varies in spectrum from monogenic and syndromic models of inheritance, usually rare, to the most common polygenic and multifactorial forms. In addition, human studies using the candidate-gene approach indicate that common genetic variants of several genes are associated with the development of CMS. Genome-wide scans have also provided several chromosomal regions associated with some of the components of CMS. In addition, through comparative genomics animal models can generate a map for candidate loci in humans and a promising approach is offered by bioinformatic tools for gene prioritization. Lastly, the involvement of genes whose products are already the targets for approved drugs, such as SLC6A4, PPARalpha and PPARgamma , in the development of CMS suggests new avenues for CMS pharmacological treatment.

  7. Familial Renal Cancer: Molecular Genetics and Surgical Management

    Directory of Open Access Journals (Sweden)

    Glen W. Barrisford

    2011-01-01

    Full Text Available Familial renal cancer (FRC is a heterogeneous disorder comprised of a variety of subtypes. Each subtype is known to have unique histologic features, genetic alterations, and response to therapy. Through the study of families affected by hereditary forms of kidney cancer, insights into the genetic basis of this disease have been identified. This has resulted in the elucidation of a number of kidney cancer gene pathways. Study of these pathways has led to the development of novel targeted molecular treatments for patients affected by systemic disease. As a result, the treatments for families affected by von Hippel-Lindau (VHL, hereditary papillary renal carcinoma (HPRC, hereditary leiomyomatosis renal cell carcinoma (HLRCC, and Birt-Hogg-Dubé (BHD are rapidly changing. We review the genetics and contemporary surgical management of familial forms of kidney cancer.

  8. Moyamoya disease and syndromes: from genetics to clinical management

    Directory of Open Access Journals (Sweden)

    Guey S

    2015-02-01

    . Revascularization surgery can be indicated, with several techniques. Characteristics of genetic moyamoya syndromes are presented, with a focus on recently reported mutations in BRCC3/MTCP1 and GUCY1A3 genes. Identification of the genes involved in moyamoya disease and several monogenic moyamoya syndromes unraveled different pathways involved in the development of this angiopathy. Studying genes and pathways involved in monogenic moyamoya syndromes may help to give insights into pathophysiological models and discover potential candidates for medical treatment strategies. Keywords: moyamoya disease, moyamoya syndrome, stroke, surgical revascularization, genetics

  9. Update on the Cytogenetics and Molecular Genetics of Chordoma

    Directory of Open Access Journals (Sweden)

    Larizza Lidia

    2005-02-01

    Full Text Available Abstract Chordoma is a rare mesenchymal tumour of complex biology for which only histologic and immunohistochemical criteria have been defined, but no biomarkers predicting the clinical outcome and response to treatment have yet been recognised. We herein review the interdisciplinary information achieved by epidemiologists, neurosurgeons and basic scientists on chordoma, usually a sporadic tumour, which also includes a small fraction of familial cases. Main focus is on the current knowledge of the genetic alterations which might pinpoint candidate genes and molecular mechanisms shared by sporadic and familiar chordomas. Due to the scarcity of the investigated tumour specimens and the multiple chromosome abnormalities found in tumours with aberrant karyotypes, conventional cytogenetics and Fluorescence In Situ Hybridization failed to detect recurrent chordoma-specific chromosomal rearrangements. Genome-wide approaches such as Comparative Genomic Hybridization (CGH are yet at an initial stage of application and should be implemented using BAC arrays either genome-wide or targeting selected genomic regions, disclosed by Loss of Heterozygosity (LOH studies. An LOH region was shown by a systematic study on a consistent number of chordomas to encompass 1p36, a genomic interval where a candidate gene was suggested to reside. Despite the rarity of multiplex families with chordoma impaired linkage studies, a chordoma locus could be mapped to chromosome 7q33 by positive lod score in three independent families. The role in chordomagenesis of the Tuberous Sclerosis Complex (TSC genes has been proved, but the extent of involvement of TSC1 and TSC2 oncosuppressors in chordoma remains to be assessed. In spite of the scarce knowledge on the genetics and molecular biology of chordoma, recent initiation of clinical trials using molecular-targeted therapy, should validate new molecular targets and predict the efficacy of a given therapy. Comparative genetic and

  10. Human fertility, molecular genetics, and natural selection in modern societies.

    Directory of Open Access Journals (Sweden)

    Felix C Tropf

    Full Text Available Research on genetic influences on human fertility outcomes such as number of children ever born (NEB or the age at first childbirth (AFB has been solely based on twin and family-designs that suffer from problematic assumptions and practical limitations. The current study exploits recent advances in the field of molecular genetics by applying the genomic-relationship-matrix based restricted maximum likelihood (GREML methods to quantify for the first time the extent to which common genetic variants influence the NEB and the AFB of women. Using data from the UK and the Netherlands (N = 6,758, results show significant additive genetic effects on both traits explaining 10% (SE = 5 of the variance in the NEB and 15% (SE = 4 in the AFB. We further find a significant negative genetic correlation between AFB and NEB in the pooled sample of -0.62 (SE = 0.27, p-value = 0.02. This finding implies that individuals with genetic predispositions for an earlier AFB had a reproductive advantage and that natural selection operated not only in historical, but also in contemporary populations. The observed postponement in the AFB across the past century in Europe contrasts with these findings, suggesting an evolutionary override by environmental effects and underscoring that evolutionary predictions in modern human societies are not straight forward. It emphasizes the necessity for an integrative research design from the fields of genetics and social sciences in order to understand and predict fertility outcomes. Finally, our results suggest that we may be able to find genetic variants associated with human fertility when conducting GWAS-meta analyses with sufficient sample size.

  11. PAX6 aniridia syndrome: clinics, genetics, and therapeutics.

    Science.gov (United States)

    Lim, Hyun Taek; Kim, Dae Hee; Kim, Hyuna

    2017-09-01

    Aniridia is a rare and panocular disorder affecting most of the ocular structures which may have significant impact on vision. The purpose of this review is to describe the clinical features, genetics, and therapeutic options for this disease and to provide an update of current knowledge and latest research findings. Aside from the ocular features, a variety of associated systemic abnormalities, including hormonal, metabolic, gastrointestinal, genitourinary, and neurologic pathologies have been reported in children with aniridia. Although mutations in PAX6 are a major cause of aniridia, genetic defects in nearby genes, such as TRIM44 or ELP4, have also been reported to cause aniridia. Recent improvement in genetic testing technique will help more rapid and precise diagnosis for aniridia. A promising therapeutic approach called nonsense suppression therapy has been introduced and successfully used in an animal model. Aniridia is a challenging disease. The progressive nature of this condition and its potential complications require continuous and life-long ophthalmologic care. Genetic diagnosis for aniridia is important for establishing definitive molecular characterization as well as identifying individuals at high risk for Wilms tumor. Recent advancement in understanding the genetic pathogenesis of this disease offers promise for the approaches to treatment.

  12. [Results and promises of genetics of cognitive impairment in schizophrenia: molecular-genetic approaches].

    Science.gov (United States)

    Alfimova, M V; Kondratiev, N V; Golimbet, V E

    2016-01-01

    This review highlights the basic paradigms and directions of molecular genetic studies of cognitive deficits in schizophrenia. Along with the traditional approach based on functional candidate genes, it covers genome-wide association studies (GWAS) for cognition in general population and schizophrenic patients, attempts to integrate GWAS results in polygenic profiles that can be used in personalized care of schizophrenic patients, and a search for biological pathways implicated in the development of cognitive impairments with bioinformatics methods. However, despite significant advances in understanding the genetic basis of the disease and a rapidly growing amount of data on genes associated with cognitive functions, most of the variability of cognitive impairments in patients remains unexplained. The data on the functional complexity of the genome accumulated in the fields of molecular biology and genetics underscore the importance of studying epigenetic mechanisms of cognitive deficits in schizophrenia.

  13. Reliable prediction of adsorption isotherms via genetic algorithm molecular simulation.

    Science.gov (United States)

    LoftiKatooli, L; Shahsavand, A

    2017-01-01

    Conventional molecular simulation techniques such as grand canonical Monte Carlo (GCMC) strictly rely on purely random search inside the simulation box for predicting the adsorption isotherms. This blind search is usually extremely time demanding for providing a faithful approximation of the real isotherm and in some cases may lead to non-optimal solutions. A novel approach is presented in this article which does not use any of the classical steps of the standard GCMC method, such as displacement, insertation, and removal. The new approach is based on the well-known genetic algorithm to find the optimal configuration for adsorption of any adsorbate on a structured adsorbent under prevailing pressure and temperature. The proposed approach considers the molecular simulation problem as a global optimization challenge. A detailed flow chart of our so-called genetic algorithm molecular simulation (GAMS) method is presented, which is entirely different from traditions molecular simulation approaches. Three real case studies (for adsorption of CO 2 and H 2 over various zeolites) are borrowed from literature to clearly illustrate the superior performances of the proposed method over the standard GCMC technique. For the present method, the average absolute values of percentage errors are around 11% (RHO-H 2 ), 5% (CHA-CO 2 ), and 16% (BEA-CO 2 ), while they were about 70%, 15%, and 40% for the standard GCMC technique, respectively.

  14. Empirical Refinements of a Molecular Genetics Learning Progression: The Molecular Constructs

    Science.gov (United States)

    Todd, Amber; Kenyon, Lisa

    2016-01-01

    This article describes revisions to four of the eight constructs of the Duncan molecular genetics learning progression [Duncan, Rogat, & Yarden, (2009)]. As learning progressions remain hypothetical models until validated by multiple rounds of empirical studies, these revisions are an important step toward validating the progression. Our…

  15. Genetic Analysis for Two Italian Siblings with Usher Syndrome and Schizophrenia

    Directory of Open Access Journals (Sweden)

    Daniela Domanico

    2012-01-01

    Full Text Available Usher syndrome is a group of autosomal recessive genetic disorders characterized by deafness, retinitis pigmentosa, and sometimes vestibular areflexia. The relationship between Usher syndrome and mental disorders, most commonly a “schizophrenia-like” psychosis, is sometimes described in the literature. The etiology of psychiatric expression of Usher syndrome is still unclear. We reported a case of two natural siblings with congenital hypoacusis, retinitis pigmentosa, and psychiatric symptoms. Clinical features and genetic analysis were also reported. We analyzed possible causes to explain the high prevalence of psychiatric manifestations in Usher syndrome: genetic factors, brain damage, and “stress-related” hypothesis.

  16. Molecular and clinical study of 61 Angelman syndrome patients

    Energy Technology Data Exchange (ETDEWEB)

    Saitoh, Shinji; Harada, Naoki; Jinno, Yoshihiro; Niikawa, Norio [Nagasaki Univ. School of Medicine (Japan); Imaizumi, Kiyoshi; Kuroki, Yoshikazu; Fukushima; Yoshimitsu; Sugimoto, Tateo; Renedo, Monica

    1994-08-15

    We analyzed 61 Angelman syndrome (AS) patients by cytogenetic and molecular techniques. On the basis of molecular findings, the patients were classified into the following 4 groups: familial cases without deletion, familial cases with submicroscopic deletion, sporadic cases with deletion, and sporadic cases without deletion. Among 53 sporadic cases, 37 (70%) had molecular deletion, which commonly extended from D15S9 to D15S12, although not all deletions were identical. Of 8 familial cases, 3 sibs from one family had a molecular deletion involving only 2 loci, D15S10 and GABRB3, which define the critical region for AS phenotypes. The parental origin of deletion, both in sporadic and familial cases, was exclusively maternal and consistent with a genomic imprinting hypothesis. Among sporadic and familial cases without deletion, no uniparental disomy was found and most of them were shown to inherit chromosomes 15 from both parents (biparental inheritance). A discrepancy between cytogenetic and molecular deletion was observed in 14 (26%) of 53 patients in whom cytogenetic analysis could be performed. Ten (43%) of 23 patients with a normal karyotype showed a molecular deletion, and 4 (13%) of 30 patients with cytogenetic deletion, del(15) (q11q13), showed no molecular deletion. Most clinical manifestations, including neurological signs and facial characteristics, were not distinct in each group except for hypopigmentation of skin or hair. Familial cases with submicroscopic deletion were not associated with hypopigmentation. These findings suggested that a gene for hypopigmentation is located outside the critical region of AS and is not imprinted. 37 refs., 2 figs., 4 tabs.

  17. Genetic predisposition syndromes: when should they be considered in the work-up of MDS?

    Science.gov (United States)

    Babushok, Daria V; Bessler, Monica

    2015-03-01

    Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders characterized by cytopenias, ineffective hematopoiesis, myelodysplasia, and an increased risk of acute myeloid leukemia (AML). While sporadic MDS is primarily a disease of the elderly, MDS in children and young and middle-aged adults is frequently associated with underlying genetic predisposition syndromes. In addition to the classic hereditary bone marrow failure syndromes (BMFS) such as Fanconi Anemia and Dyskeratosis Congenita, in recent years there has been an increased awareness of non-syndromic familial MDS/AML predisposition syndromes such as those caused by mutations in GATA2, RUNX1, CEBPA, and SRP72 genes. Here, we will discuss the importance of recognizing an underlying genetic predisposition syndrome a patient with MDS, will review clinical scenarios when genetic predisposition should be considered, and will provide a practical overview of the common BMFS and familial MDS/AML syndromes which may be encountered in adult patients with MDS. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Development of a genomic DNA reference material panel for Rett syndrome (MECP2-related disorders) genetic testing.

    Science.gov (United States)

    Kalman, Lisa V; Tarleton, Jack C; Percy, Alan K; Aradhya, Swaroop; Bale, Sherri; Barker, Shannon D; Bayrak-Toydemir, Pinar; Bridges, Christina; Buller-Burckle, Arlene M; Das, Soma; Iyer, Ramaswamy K; Vo, Timothy D; Zvereff, Val V; Toji, Lorraine H

    2014-03-01

    Rett syndrome is a dominant X-linked disorder caused by point mutations (approximately 80%) or by deletions or insertions (approximately 15% to 18%) in the MECP2 gene. It is most common in females but lethal in males, with a distinctly different phenotype. Rett syndrome patients have severe neurological and behavioral problems. Clinical genetic testing laboratories commonly use characterized genomic DNA reference materials to assure the quality of the testing process; however, none are commercially available for MECP2 genetic testing. The Centers for Disease Control and Prevention's Genetic Testing Reference Material Coordination Program, in collaboration with the genetic testing community and the Coriell Cell Repositories, established 27 new cell lines and characterized the MECP2 mutations in these and in 8 previously available cell lines. DNA samples from the 35 cell lines were tested by eight clinical genetic testing laboratories using DNA sequence analysis and methods to assess copy number (multiplex ligation-dependent probe amplification, semiquantitative PCR, or array-based comparative genomic hybridization). The eight common point mutations known to cause approximately 60% of Rett syndrome cases were identified, as were other MECP2 variants, including deletions, duplications, and frame shift and splice-site mutations. Two of the 35 samples were from males with MECP2 duplications. These MECP2 and other characterized genomic DNA samples are publicly available from the NIGMS Repository at the Coriell Cell Repositories. Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  19. Prader-Willi syndrome: cycloid psychosis in a genetic subtype?

    Science.gov (United States)

    Verhoeven, W M A; Tuinier, S; Curfs, L M G

    2003-02-01

    Prader-Willi syndrome (PWS) is a genetically determined disorder associated with the loss of the paternal contribution to the proximal part of the long arm of chromosome 15. Its pathophysiology is dominated by hypothalamic dysfunctions. The psychopathological phenotype comprises affective and psychotic symptoms as well as an increase of pre-existent obsessive-compulsive behaviors. The present study comprises 19 PWS patients who were referred for neuropsychiatric evaluation because of psychotic deterioration. Patients were assessed by using the elements of semistructured symptom checklists. In the majority a genetic analysis was performed to detect the underlying chromosomal defect. In 16 of the 19 patients a diagnosis of cycloid psychosis could be established. The other three showed a bipolar affective disorder. Of the psychotic patients, 11 were diagnosed as UPD and one as del 15q11-13. The remaining four patients were diagnosed clinically. For various reasons the genetic etiology could not be established. In PWS patients with a psychotic disorder (cycloid psychosis) a disproportional number of UPD is found.

  20. Genetic and molecular basis of diabetic foot ulcers: Clinical review.

    Science.gov (United States)

    Jhamb, Shaurya; Vangaveti, Venkat N; Malabu, Usman H

    2016-11-01

    Diabetic Foot Ulcers (DFUs) are major complications associated with diabetes and often correlate with peripheral neuropathy, trauma and peripheral vascular disease. It is necessary to understand the molecular and genetic basis of diabetic foot ulcers in order to tailor patient centred care towards particular patient groups. This review aimed to evaluate whether current literature was indicative of an underlying molecular and genetic basis for DFUs and to discuss clinical applications. From a molecular perspective, wound healing is a process that transpires following breach of the skin barrier and is usually mediated by growth factors and cytokines released by specialised cells activated by the immune response, including fibroblasts, endothelial cells, phagocytes, platelets and keratinocytes. Growth factors and cytokines are fundamental in the organisation of the molecular processes involved in making cutaneous wound healing possible. There is a significant role for single nucleotide polymorphism (SNPs) in the fluctuation of these growth factors and cytokines in DFUs. Furthermore, recent evidence suggests a key role for epigenetic mechanisms such as DNA methylation from long standing hyperglycemia and non-coding RNAs in the complex interplay between genes and the environment. Genetic factors and ethnicity can also play a significant role in the development of diabetic neuropathy leading to DFUs. Clinically, interventions which have improved outcomes for people with DFUs or those at risk of DFUs include some systemic therapeutic drug interventions which improve microvascular blood flow, surgical interventions, human growth factors, and hyperbaric oxygen therapy, negative pressure wound therapy, skin replacement or shockwave therapy and the use of topical treatments. Future treatment modalities including stem cell and gene therapies are promising in the therapeutic approach to prevent the progression of chronic diabetic complications. Copyright © 2016 Tissue

  1. The Molecular Genetic Architecture of Self-Employment

    Science.gov (United States)

    van der Loos, Matthijs J. H. M.; Rietveld, Cornelius A.; Eklund, Niina; Koellinger, Philipp D.; Rivadeneira, Fernando; Abecasis, Gonçalo R.; Ankra-Badu, Georgina A.; Baumeister, Sebastian E.; Benjamin, Daniel J.; Biffar, Reiner; Blankenberg, Stefan; Boomsma, Dorret I.; Cesarini, David; Cucca, Francesco; de Geus, Eco J. C.; Dedoussis, George; Deloukas, Panos; Dimitriou, Maria; Eiriksdottir, Guðny; Eriksson, Johan; Gieger, Christian; Gudnason, Vilmundur; Höhne, Birgit; Holle, Rolf; Hottenga, Jouke-Jan; Isaacs, Aaron; Järvelin, Marjo-Riitta; Johannesson, Magnus; Kaakinen, Marika; Kähönen, Mika; Kanoni, Stavroula; Laaksonen, Maarit A.; Lahti, Jari; Launer, Lenore J.; Lehtimäki, Terho; Loitfelder, Marisa; Magnusson, Patrik K. E.; Naitza, Silvia; Oostra, Ben A.; Perola, Markus; Petrovic, Katja; Quaye, Lydia; Raitakari, Olli; Ripatti, Samuli; Scheet, Paul; Schlessinger, David; Schmidt, Carsten O.; Schmidt, Helena; Schmidt, Reinhold; Senft, Andrea; Smith, Albert V.; Spector, Timothy D.; Surakka, Ida; Svento, Rauli; Terracciano, Antonio; Tikkanen, Emmi; van Duijn, Cornelia M.; Viikari, Jorma; Völzke, Henry; Wichmann, H. -Erich; Wild, Philipp S.; Willems, Sara M.; Willemsen, Gonneke; van Rooij, Frank J. A.; Groenen, Patrick J. F.; Uitterlinden, André G.; Hofman, Albert; Thurik, A. Roy

    2013-01-01

    Economic variables such as income, education, and occupation are known to affect mortality and morbidity, such as cardiovascular disease, and have also been shown to be partly heritable. However, very little is known about which genes influence economic variables, although these genes may have both a direct and an indirect effect on health. We report results from the first large-scale collaboration that studies the molecular genetic architecture of an economic variable–entrepreneurship–that was operationalized using self-employment, a widely-available proxy. Our results suggest that common SNPs when considered jointly explain about half of the narrow-sense heritability of self-employment estimated in twin data (σg 2/σP 2 = 25%, h 2 = 55%). However, a meta-analysis of genome-wide association studies across sixteen studies comprising 50,627 participants did not identify genome-wide significant SNPs. 58 SNPs with pentrepreneurship reveal significant associations. Finally, SNP-based genetic scores that use results from the meta-analysis capture less than 0.2% of the variance in self-employment in an independent sample (p≥0.039). Our results are consistent with a highly polygenic molecular genetic architecture of self-employment, with many genetic variants of small effect. Although self-employment is a multi-faceted, heavily environmentally influenced, and biologically distal trait, our results are similar to those for other genetically complex and biologically more proximate outcomes, such as height, intelligence, personality, and several diseases. PMID:23593239

  2. Molecular genetics and livestock selection. Approaches, opportunities and risks

    International Nuclear Information System (INIS)

    Williams, J.L.

    2005-01-01

    Following domestication, livestock were selected both naturally through adaptation to their environments and by man so that they would fulfil a particular use. As selection methods have become more sophisticated, rapid progress has been made in improving those traits that are easily measured. However, selection has also resulted in decreased diversity. In some cases, improved breeds have replaced local breeds, risking the loss of important survival traits. The advent of molecular genetics provides the opportunity to identify the genes that control particular traits by a gene mapping approach. However, as with selection, the early mapping studies focused on traits that are easy to measure. Where molecular genetics can play a valuable role in livestock production is by providing the means to select effectively for traits that are difficult to measure. Identifying the genes underpinning particular traits requires a population in which these traits are segregating. Fortunately, several experimental populations have been created that have allowed a wide range of traits to be studied. Gene mapping work in these populations has shown that the role of particular genes in controlling variation in a given trait can depend on the genetic background. A second finding is that the most favourable alleles for a trait may in fact. be present in animals that perform poorly for the trait. In the long term, knowledge of -the genes controlling particular traits, and the way they interact with the genetic background, will allow introgression between breeds and the assembly of genotypes that are best suited to particular environments, producing animals with the desired characteristics. If used wisely, this approach will maintain genetic diversity while improving performance over a wide range of desired traits. (author)

  3. The molecular genetic architecture of self-employment.

    Directory of Open Access Journals (Sweden)

    Matthijs J H M van der Loos

    Full Text Available Economic variables such as income, education, and occupation are known to affect mortality and morbidity, such as cardiovascular disease, and have also been shown to be partly heritable. However, very little is known about which genes influence economic variables, although these genes may have both a direct and an indirect effect on health. We report results from the first large-scale collaboration that studies the molecular genetic architecture of an economic variable-entrepreneurship-that was operationalized using self-employment, a widely-available proxy. Our results suggest that common SNPs when considered jointly explain about half of the narrow-sense heritability of self-employment estimated in twin data (σ(g(2/σ(P(2 = 25%, h(2 = 55%. However, a meta-analysis of genome-wide association studies across sixteen studies comprising 50,627 participants did not identify genome-wide significant SNPs. 58 SNPs with p<10(-5 were tested in a replication sample (n = 3,271, but none replicated. Furthermore, a gene-based test shows that none of the genes that were previously suggested in the literature to influence entrepreneurship reveal significant associations. Finally, SNP-based genetic scores that use results from the meta-analysis capture less than 0.2% of the variance in self-employment in an independent sample (p≥0.039. Our results are consistent with a highly polygenic molecular genetic architecture of self-employment, with many genetic variants of small effect. Although self-employment is a multi-faceted, heavily environmentally influenced, and biologically distal trait, our results are similar to those for other genetically complex and biologically more proximate outcomes, such as height, intelligence, personality, and several diseases.

  4. Genetic analysis of a Chinese family with members affected with Usher syndrome type II and Waardenburg syndrome type IV.

    Science.gov (United States)

    Wang, Xueling; Lin, Xiao-Jiang; Tang, Xiangrong; Chai, Yong-Chuan; Yu, De-Hong; Chen, Dong-Ye; Wu, Hao

    2017-11-01

    The purpose of this study was to identify the genetic causes of a family presenting with multiple symptoms overlapping Usher syndrome type II (USH2) and Waardenburg syndrome type IV (WS4). Targeted next-generation sequencing including the exon and flanking intron sequences of 79 deafness genes was performed on the proband. Co-segregation of the disease phenotype and the detected variants were confirmed in all family members by PCR amplification and Sanger sequencing. The affected members of this family had two different recessive disorders, USH2 and WS4. By targeted next-generation sequencing, we identified that USH2 was caused by a novel missense mutation, p.V4907D in GPR98; whereas WS4 due to p.V185M in EDNRB. This is the first report of homozygous p.V185M mutation in EDNRB in patient with WS4. This study reported a Chinese family with multiple independent and overlapping phenotypes. In condition, molecular level analysis was efficient to identify the causative variant p.V4907D in GPR98 and p.V185M in EDNRB, also was helpful to confirm the clinical diagnosis of USH2 and WS4. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Genetic diagnosis and genetic counseling for androgen-insensitivity syndrome: a report of three cases.

    Science.gov (United States)

    Yamaguchi, Masatoshi; Sameshima, Hiroshi; Ikenoue, Tyuyomu

    2014-03-01

    In order to verify androgen-insensitivity syndrome (AIS) for three individuals and their mothers, genetic diagnosis was performed after genetic counseling. Polymerase chain reaction analysis was used for each exon of the androgen receptor (AR Xq11-q12) gene. The amplified DNA fragments were detected by gel electrophoresis. The DNA fragments were sequenced and their sequences were compared with those in a database (The Androgen Receptor Gene Mutations Database World Wide Web Server). A missense mutation was identified in exon 7 in case 1, deletions of exons 1 and 2 were identified in case 2, and a nonsense mutation was identified in the triplet repeat region of exon 1 in case 3. The mothers of the patients were also verified to be carriers of the mutations. Genetic diagnosis is a very useful method for diagnosing AIS. However, genetic counseling, including emotional support for the mother, is an essential component of genetic diagnosis. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

  6. A consortium approach to molecular genetic services. Scottish Molecular Genetics Consortium.

    OpenAIRE

    Brock, D J

    1990-01-01

    The four Scottish university medical genetics centres formed a consortium in 1985 to provide a DNA based service in prenatal diagnosis, carrier detection, and predictive testing for a range of Mendelian disorders. Each centre took sole responsibility for laboratory analyses of an assigned set of disorders, while families continued to be investigated and patients counselled within their own areas. DNA was extracted from relevant tissues in the centre most convenient to the family member and th...

  7. Molecular genetic identification of some wheat cultivars in the sudan

    International Nuclear Information System (INIS)

    Mekki, I. I; El Amin, H. B.

    2002-01-01

    Four wheat (Triticum aestivum L.) cultivars, namely condor, El-Nellene, Wadi El Neil and Debeira were characterized on biochemical and molecular bases. The biochemical ones were protein-banding patterns, using sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and isozymes to identify the biochemical genetic fingerprint of the four cultivars. Water-soluble protein-banding pattern showed no polymorphisms among the tested cultivars. The data from starch gel electrophoresis of enzymes, malate dehydrogenase (MDH), esterase (EST) and acid phosphate (ACPH) showed that the cultivars are monomorphic. Further trials to identify the molecular genetic fingerprints of the studied cultivars were carried out using RAPD-PCR twenty-five primers were tested to perform. RAPD-PCR analysis. From the PCR products, a phylogenetic map, i.e, dendrogram, was constructed for the studied cultivars which depicted tow groups. The first group contained Wadi El Neil and Deberia with 48.4% similarity, and the second group contained Condor and El Neileen with 100% similarity. There was no similarity between Condor and Debeira (100% dissimilarity). Therefor, these data can be used subsequently for genetic engineering research and for wheat breeding programmes in the Sudan.(Author)

  8. Molecular pathogenesis of long QT syndrome type 1

    Directory of Open Access Journals (Sweden)

    Jie Wu, PhD

    2016-10-01

    Full Text Available Long QT syndrome type 1 (LQT1 is a subtype of a congenital cardiac syndrome caused by mutation in the KCNQ1 gene, which encodes the α-subunit of the slow component of delayed rectifier K+ current (IKs channel. Arrhythmias in LQT1 are characterized by prolongation of the QT interval on ECG, as well as the occurrence of life-threatening cardiac events, frequently triggered by adrenergic stimuli (e.g., physical or emotional stress. During the past two decades, much advancement has been made in understanding the molecular pathogenesis underlying LQT1. Uncovering the genotype-phenotype correlations in LQT1 is of clinical importance to better understand the gene-specific differences that may influence the propensity for developing life-threatening arrhythmias under specific conditions. Elucidation of these mechanisms will also help to improve the diagnosis and management of this cardiac disorder based on gene-specific considerations. This review describes the current medical consensus and recent developments regarding the molecular pathogenesis of LQT1 and provides a novel insight into the adrenergic regulation of this disease.

  9. Fishing the molecular bases of Treacher Collins syndrome.

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    Andrea M J Weiner

    Full Text Available Treacher Collins syndrome (TCS is an autosomal dominant disorder of craniofacial development, and mutations in the TCOF1 gene are responsible for over 90% of TCS cases. The knowledge about the molecular mechanisms responsible for this syndrome is relatively scant, probably due to the difficulty of reproducing the pathology in experimental animals. Zebrafish is an emerging model for human disease studies, and we therefore assessed it as a model for studying TCS. We identified in silico the putative zebrafish TCOF1 ortholog and cloned the corresponding cDNA. The derived polypeptide shares the main structural domains found in mammals and amphibians. Tcof1 expression is restricted to the anterior-most regions of zebrafish developing embryos, similar to what happens in mouse embryos. Tcof1 loss-of-function resulted in fish showing phenotypes similar to those observed in TCS patients, and enabled a further characterization of the mechanisms underlying craniofacial malformation. Besides, we initiated the identification of potential molecular targets of treacle in zebrafish. We found that Tcof1 loss-of-function led to a decrease in the expression of cellular proliferation and craniofacial development. Together, results presented here strongly suggest that it is possible to achieve fish with TCS-like phenotype by knocking down the expression of the TCOF1 ortholog in zebrafish. This experimental condition may facilitate the study of the disease etiology during embryonic development.

  10. Fishing the molecular bases of Treacher Collins syndrome.

    Science.gov (United States)

    Weiner, Andrea M J; Scampoli, Nadia L; Calcaterra, Nora B

    2012-01-01

    Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development, and mutations in the TCOF1 gene are responsible for over 90% of TCS cases. The knowledge about the molecular mechanisms responsible for this syndrome is relatively scant, probably due to the difficulty of reproducing the pathology in experimental animals. Zebrafish is an emerging model for human disease studies, and we therefore assessed it as a model for studying TCS. We identified in silico the putative zebrafish TCOF1 ortholog and cloned the corresponding cDNA. The derived polypeptide shares the main structural domains found in mammals and amphibians. Tcof1 expression is restricted to the anterior-most regions of zebrafish developing embryos, similar to what happens in mouse embryos. Tcof1 loss-of-function resulted in fish showing phenotypes similar to those observed in TCS patients, and enabled a further characterization of the mechanisms underlying craniofacial malformation. Besides, we initiated the identification of potential molecular targets of treacle in zebrafish. We found that Tcof1 loss-of-function led to a decrease in the expression of cellular proliferation and craniofacial development. Together, results presented here strongly suggest that it is possible to achieve fish with TCS-like phenotype by knocking down the expression of the TCOF1 ortholog in zebrafish. This experimental condition may facilitate the study of the disease etiology during embryonic development.

  11. Genetic Analysis of 'PAX6-Negative' Individuals with Aniridia or Gillespie Syndrome.

    Directory of Open Access Journals (Sweden)

    Morad Ansari

    Full Text Available We report molecular genetic analysis of 42 affected individuals referred with a diagnosis of aniridia who previously screened as negative for intragenic PAX6 mutations. Of these 42, the diagnoses were 31 individuals with aniridia and 11 individuals referred with a diagnosis of Gillespie syndrome (iris hypoplasia, ataxia and mild to moderate developmental delay. Array-based comparative genomic hybridization identified six whole gene deletions: four encompassing PAX6 and two encompassing FOXC1. Six deletions with plausible cis-regulatory effects were identified: five that were 3' (telomeric to PAX6 and one within a gene desert 5' (telomeric to PITX2. Sequence analysis of the FOXC1 and PITX2 coding regions identified two plausibly pathogenic de novo FOXC1 missense mutations (p.Pro79Thr and p.Leu101Pro. No intragenic mutations were detected in PITX2. FISH mapping in an individual with Gillespie-like syndrome with an apparently balanced X;11 reciprocal translocation revealed disruption of a gene at each breakpoint: ARHGAP6 on the X chromosome and PHF21A on chromosome 11. In the other individuals with Gillespie syndrome no mutations were identified in either of these genes, or in HCCS which lies close to the Xp breakpoint. Disruption of PHF21A has previously been implicated in the causation of intellectual disability (but not aniridia. Plausibly causative mutations were identified in 15 out of 42 individuals (12/32 aniridia; 3/11 Gillespie syndrome. Fourteen of these mutations presented in the known aniridia genes; PAX6, FOXC1 and PITX2. The large number of individuals in the cohort with no mutation identified suggests greater locus heterogeneity may exist in both isolated and syndromic aniridia than was previously appreciated.

  12. Understanding the Molecular Genetics of Basal Cell Carcinoma

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    Cristina Pellegrini

    2017-11-01

    Full Text Available Basal cell carcinoma (BCC is the most common human cancer and represents a growing public health care problem. Several tumor suppressor genes and proto-oncogenes have been implicated in BCC pathogenesis, including the key components of the Hedgehog pathway, PTCH1 and SMO, the TP53 tumor suppressor, and members of the RAS proto-oncogene family. Aberrant activation of the Hedgehog pathway represents the molecular driver in basal cell carcinoma pathogenesis, with the majority of BCCs carrying somatic point mutations, mainly ultraviolet (UV-induced, and/or copy-loss of heterozygosis in the PTCH1 gene. Recent advances in sequencing technology allowed genome-scale approaches to mutation discovery, identifying new genes and pathways potentially involved in BCC carcinogenesis. Mutational and functional analysis suggested PTPN14 and LATS1, both effectors of the Hippo–YAP pathway, and MYCN as new BCC-associated genes. In addition, emerging reports identified frequent non-coding mutations within the regulatory promoter sequences of the TERT and DPH3-OXNAD1 genes. Thus, it is clear that a more complex genetic network of cancer-associated genes than previously hypothesized is involved in BCC carcinogenesis, with a potential impact on the development of new molecular targeted therapies. This article reviews established knowledge and new hypotheses regarding the molecular genetics of BCC pathogenesis.

  13. Understanding the Molecular Genetics of Basal Cell Carcinoma

    Science.gov (United States)

    Maturo, Maria Giovanna; Ciciarelli, Valeria; Gutiérrez García-Rodrigo, Carlota; Fargnoli, Maria Concetta

    2017-01-01

    Basal cell carcinoma (BCC) is the most common human cancer and represents a growing public health care problem. Several tumor suppressor genes and proto-oncogenes have been implicated in BCC pathogenesis, including the key components of the Hedgehog pathway, PTCH1 and SMO, the TP53 tumor suppressor, and members of the RAS proto-oncogene family. Aberrant activation of the Hedgehog pathway represents the molecular driver in basal cell carcinoma pathogenesis, with the majority of BCCs carrying somatic point mutations, mainly ultraviolet (UV)-induced, and/or copy-loss of heterozygosis in the PTCH1 gene. Recent advances in sequencing technology allowed genome-scale approaches to mutation discovery, identifying new genes and pathways potentially involved in BCC carcinogenesis. Mutational and functional analysis suggested PTPN14 and LATS1, both effectors of the Hippo–YAP pathway, and MYCN as new BCC-associated genes. In addition, emerging reports identified frequent non-coding mutations within the regulatory promoter sequences of the TERT and DPH3-OXNAD1 genes. Thus, it is clear that a more complex genetic network of cancer-associated genes than previously hypothesized is involved in BCC carcinogenesis, with a potential impact on the development of new molecular targeted therapies. This article reviews established knowledge and new hypotheses regarding the molecular genetics of BCC pathogenesis. PMID:29165358

  14. Phenotypic and Molecular Convergence of 2q23.1 Deletion Syndrome with Other Neurodevelopmental Syndromes Associated with Autism Spectrum Disorder

    Science.gov (United States)

    Mullegama, Sureni V.; Alaimo, Joseph T.; Chen, Li; Elsea, Sarah H.

    2015-01-01

    Roughly 20% of autism spectrum disorders (ASD) are syndromic with a well-established genetic cause. Studying the genes involved can provide insight into the molecular and cellular mechanisms of ASD. 2q23.1 deletion syndrome (causative gene, MBD5) is a recently identified genetic neurodevelopmental disorder associated with ASD. Mutations in MBD5 have been found in ASD cohorts. In this study, we provide a phenotypic update on the prevalent features of 2q23.1 deletion syndrome, which include severe intellectual disability, seizures, significant speech impairment, sleep disturbance, and autistic-like behavioral problems. Next, we examined the phenotypic, molecular, and network/pathway relationships between nine neurodevelopmental disorders associated with ASD: 2q23.1 deletion Rett, Angelman, Pitt-Hopkins, 2q23.1 duplication, 5q14.3 deletion, Kleefstra, Kabuki make-up, and Smith-Magenis syndromes. We show phenotypic overlaps consisting of intellectual disability, speech delay, seizures, sleep disturbance, hypotonia, and autistic-like behaviors. Molecularly, MBD5 possibly regulates the expression of UBE3A, TCF4, MEF2C, EHMT1 and RAI1. Network analysis reveals that there could be indirect protein interactions, further implicating function for these genes in common pathways. Further, we show that when MBD5 and RAI1 are haploinsufficient, they perturb several common pathways that are linked to neuronal and behavioral development. These findings support further investigations into the molecular and pathway relationships among genes linked to neurodevelopmental disorders and ASD, which will hopefully lead to common points of regulation that may be targeted toward therapeutic intervention. PMID:25853262

  15. Phenotypic and Molecular Convergence of 2q23.1 Deletion Syndrome with Other Neurodevelopmental Syndromes Associated with Autism Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Sureni V. Mullegama

    2015-04-01

    Full Text Available Roughly 20% of autism spectrum disorders (ASD are syndromic with a well-established genetic cause. Studying the genes involved can provide insight into the molecular and cellular mechanisms of ASD. 2q23.1 deletion syndrome (causative gene, MBD5 is a recently identified genetic neurodevelopmental disorder associated with ASD. Mutations in MBD5 have been found in ASD cohorts. In this study, we provide a phenotypic update on the prevalent features of 2q23.1 deletion syndrome, which include severe intellectual disability, seizures, significant speech impairment, sleep disturbance, and autistic-like behavioral problems. Next, we examined the phenotypic, molecular, and network/pathway relationships between nine neurodevelopmental disorders associated with ASD: 2q23.1 deletion Rett, Angelman, Pitt-Hopkins, 2q23.1 duplication, 5q14.3 deletion, Kleefstra, Kabuki make-up, and Smith-Magenis syndromes. We show phenotypic overlaps consisting of intellectual disability, speech delay, seizures, sleep disturbance, hypotonia, and autistic-like behaviors. Molecularly, MBD5 possibly regulates the expression of UBE3A, TCF4, MEF2C, EHMT1 and RAI1. Network analysis reveals that there could be indirect protein interactions, further implicating function for these genes in common pathways. Further, we show that when MBD5 and RAI1 are haploinsufficient, they perturb several common pathways that are linked to neuronal and behavioral development. These findings support further investigations into the molecular and pathway relationships among genes linked to neurodevelopmental disorders and ASD, which will hopefully lead to common points of regulation that may be targeted toward therapeutic intervention.

  16. Sudden Infant Death Syndrome and the Genetics of Inflammation

    Science.gov (United States)

    Ferrante, Linda; Opdal, Siri Hauge

    2015-01-01

    Several studies report signs of slight infection prior to death in cases of sudden infant death syndrome (SIDS). Based on this, a hypothesis of an altered immunological homeostasis has been postulated. The cytokines are important cellular mediators that are crucial for infant health by regulating cell activity during the inflammatory process. The pro-inflammatory cytokines favor inflammation; the most important of these are IL-1α, IL-1β, IL-6, IL-8, IL-12, IL-18, TNF-α, and IFN-γ. These cytokines are controlled by the anti-inflammatory cytokines. This is accomplished by reducing the pro-inflammatory cytokine production, and thus counteracts their biological effect. The major anti-inflammatory cytokines are interleukin-1 receptor antagonist (IL-1ra), IL-4, IL-10, IL-11, and IL-13. The last decade there has been focused on genetic studies within genes that are important for the immune system, for SIDS with a special interest of the genes encoding the cytokines. This is because the cytokine genes are considered to be the genes most likely to explain the vulnerability to infection, and several studies have investigated these genes in an attempt to uncover associations between SIDS and different genetic variants. So far, the genes encoding IL-1, IL-6, IL-10, and TNF-α are the most investigated within SIDS research, and several studies indicate associations between specific variants of these genes and SIDS. Taken together, this may indicate that in at least a subset of SIDS predisposing genetic variants of the immune genes are involved. However, the immune system and the cytokine network are complex, and more studies are needed in order to better understand the interplay between different genetic variations and how this may contribute to an unfavorable immunological response. PMID:25750641

  17. Sudden infant death syndrome and the genetics of inflammation

    Directory of Open Access Journals (Sweden)

    Linda eFerrante

    2015-02-01

    Full Text Available Several studies report signs of slight infection prior to death in cases of sudden infant death syndrome (SIDS. Based on this, a hypothesis of an altered immunological homeostasis has been postulated. The cytokines are important cellular mediators that are crucial for infant health by regulating cell activity during the inflammatory process. The pro-inflammatory cytokines favor inflammation; the most important of these are IL-1α, IL-1β, IL-6, IL-8, IL-12, IL-18, TNF-α and IFN-γ. These cytokines are controlled by the anti-inflammatory cytokines. This is accomplished by reducing the pro-inflammatory cytokine production, and thus counteracts their biological effect. The major anti-inflammatory cytokines are interleukin 1 receptor antagonist (IL-1ra, IL-4, IL-10, IL-11, and IL-13. The last decade there has been focus on genetic studies within genes that are important for the immune system, for SIDS with a special interest of the genes encoding the cytokines. This is because the cytokine genes are considered to be the genes most likely to explain the vulnerability to infection, and several studies have investigated these genes in an attempt to uncover associations between SIDS and different genetic variants. So far the genes encoding IL-1, IL-6, IL-10 and TNF-α are the most investigated within SIDS research, and several studies indicates associations between specific variants of these genes and SIDS. Taken together this may indicate that in at least a subset of SIDS predisposing genetic variants of the immune genes are involved. However, the immune system and the cytokine network are complex, and more studies are needed in order to better understand the interplay between different genetic variations and how this may contribute to an unfavorable immunological response.

  18. Genetic and molecular dissection of naturally occurring variations in rice

    Energy Technology Data Exchange (ETDEWEB)

    Yano, Masahiro [National Institute of Agrobiological Sciences, Tsukuba, Ibaraki (Japan)

    2002-02-01

    The progress for structural analysis of the rice genome has allowed us to embark on the sequencing of the whole rice genome. Resources - genetic markers, sequence data, and genomic clones - derived from many efforts will be used for the functional analysis of rice genes in the next decade. Although artificially induced variations, such as mutants, have been used mainly for genetic and physiological studies in rice and other plant species, the development of DNA markers has made possible access to naturally occurring allelic variations underlying complex traits. Such analysis is often referred to as quantitative traits locus (QTL) analysis. Many QTLs have been mapped for many complex traits in rice. During the analyses of several quantitative traits by the DNA marker-assisted strategy, two questions about QTL analysis have been raised: 1) Does a QTL represent a single Mendelian locus or a cluster of multiple loci? 2) Is it possible to precisely map a QTL and identify QTLs at the molecular level using map-based or other strategies? To answer these questions, a series of analyses on heading date, including the identification of putative QTLs, characterization and fine mapping of QTLs using nearly isogenic lines (NILs), and identification of genes at QTLs for heading date by the map-based strategy has been performed. In addition, several primary permanent mapping populations and secondary genetic resources, such as chromosomal segmental substitution lines, have been developed to facilitate the genetic analysis of naturally occurring allelic variation. (M. Suetake)

  19. A mother and son with Noonan syndrome resulting from a PTPN11 mutation: first report of molecularly proven cases from Turkey.

    NARCIS (Netherlands)

    Demir, K.; Yntema, H.G.; Altincik, A.; Bober, E.

    2010-01-01

    Noonan syndrome is an autosomal dominant disorder characterized by short stature, typical craniofacial features, and congenital heart defects. The underlying genetic defects were not clear until 2001. This report is the first to describe a molecular analysis and associated clinical features of a

  20. Genetics and aging; the Werner syndrome as a segmental progeroid syndrome.

    Science.gov (United States)

    Martin, G M

    1985-01-01

    The maximum lifespan potential is a constitutional feature of speciation and must be subject to polygenic controls acting both in the domain of development and in the domain of the maintenance of macromolecular integrity. The enormous genetic heterogeneity that characterizes our own species, the complexities of numerous nature-nurture interactions, and the quantitative and qualitative variations of the senescent phenotype that are observed suggest that precise patterns of aging in each of us may be unique. Patterns of aging may also differ sharply among species (for example, semelparous vs. multiparous mammals). Some potential common denominators, however, allow one to identify progeroid syndromes in man that could lead to the elucidation of important pathways of gene action. (The suffix "-oid" means "like"; it does not mean identity.) Unimodal progeroid syndromes (eg., familial dementia of the Alzheimer type, an autosomal dominant) can help us understand the pathogenesis of a particular aspect of the senescent phenotype of man. Segmental progeroid syndromes (eg. the Werner syndrome, an autosomal recessive) may be relevant to multiple aspects of the senescent phenotype. Some results of research on the Werner syndrome may be interpreted as support for "peripheral" as opposed to "central" theories of aging; they are consistent with the view that gene action in the domain of development (adolescence, in this instance) can set the stage for patterns of aging in the adult; they point to the importance of mesenchymal cell populations in the pathogenesis of age-related disorders; finally, they underscore the role of chromosomal instability, especially in the pathogenesis of neoplasia.

  1. Fragile X syndrome: a review of clinical and molecular diagnoses.

    Science.gov (United States)

    Ciaccio, Claudia; Fontana, Laura; Milani, Donatella; Tabano, Silvia; Miozzo, Monica; Esposito, Susanna

    2017-04-19

    Fragile X Syndrome (FXS) is the second cause of intellectual disability after Down syndrome and the most prevalent cause of intellectual disability in males, affecting 1:5000-7000 men and 1:4000-6000 women. It is caused by an alteration of the FMR1 gene, which maps at the Xq27.3 band: more than 99% of individuals have a CGG expansion (>200 triplets) in the 5' UTR of the gene, and FMR1 mutations and duplication/deletion are responsible for the remaining (<1%) molecular diagnoses of FXS. The aim of this review was to gather the current clinical and molecular knowledge about FXS to provide clinicians with a tool to guide the initial assessment and follow-up of FXS and to offer to laboratory workers and researchers an update about the current diagnostic procedures. FXS is a well-known condition; however, most of the studies thus far have focused on neuropsychiatric features. Unfortunately, some of the available studies have limitations, such as the paucity of patients enrolled or bias due to the collection of the data in a single-country population, which may be not representative of the average global FXS population. In recent years, insight into the adult presentation of the disease has progressively increased. Pharmacological treatment of FXS is essentially symptom based, but the growing understanding of the molecular and biological mechanisms of the disease are paving the way to targeted therapy, which may reverse the effects of FMRP deficiency and be a real cure for the disease itself, not just its symptoms. The clinical spectrum of FXS is wide, presenting not only as an isolated intellectual disability but as a multi-systemic condition, involving predominantly the central nervous system but potentially affecting any apparatus. Given the relative high frequency of the condition and its complex clinical management, FXS appears to have an important economic and social burden.

  2. Classical and molecular genetics of malignant melanoma and dysplastic naevi

    International Nuclear Information System (INIS)

    Traupe, H.; Macher, E.

    1988-01-01

    The authors conclude that the prevailing concept of monogenic autosomaldominant inheritance of dysplastic naevi and familial melanoma is not compatible with the principles of formal (Mendelian) genetics. The concept of polygenic inheritance offers instead a sound basis to explain familial aggregation of dysplastic naevi and melanoma. The various genes involved have not yet been identified at the molecular level. The recent advances made possible by modern DNA technology have given us a new view of carcinogenesis. In human malignant melanoma, chromosomes 1, 6, 7 are of particular interest and oncogenes located on these chromosomes may be involved with the initiation, promotion and progression of melanoma. Carcinogenesis is viewed as a multistep process and even tumour initiation requires the input of at least two independent oncogenes. Molecular genetics thus adds an important argument for the existence of a polygenic predisposition to melanoma. The concept of polygenic inheritance is not restricted to familial melanoma, but implies that all melanomas basically share the same predisposition and are due to similar genetic mechanisms. In some patients an inherited genetic predisposition is of great importance, whereas in others (the majority) environmental factors (e.g. UV-light-induced mutations) will be the cause of initial steps in the malignant transformation. The concept of polygenic inheritance has consequences for the management of our patients. In contrast to simple Mendelian inheritance, the risk for dysplastic naevi and melanoma is not constantly 50%, but increases with the number of family members already affected. Persons belonging to families with more that 2 affected close relatives should be considered at high risk regardless of the dysplastic naevus status. Strict surveillance of this patient group is warranted for melanoma prevention

  3. A new view on molecular genetic features of stomach cancer

    Directory of Open Access Journals (Sweden)

    A. A. Mashukov

    2017-10-01

    Full Text Available The purpose of this article was to write a literature review on the possibility of genetic typing of patients with stomach cancer at the current stage of the domestic molecular genetic laboratory service development. Materials and мethods. The combination of molecular factors in gastric cancer (GC used in the work was based on their relevance in clinical and experimental studies in case of GC over the last 10 years. The frequency of their use in foreign and domestic research works cited by PubMed and Google Scholar Systems, as well as our own research, was estimated. Results. Signs of genetically-stable stomach cancer (GSGC were: a combination of low, below 10 %, p53 oncoprotein expression, the presence of at least weak VEGFR-C expression, a high, more than 20 %, proliferative tumor index. Chromosomal-unstable tumors were characterized not only by the presence of positive expression of crbB2, but also by more than 10 % expression of p53 oncoprotein and complete absence of VEGFR-C expression. Microsatellite-unstable GC (MUGC was characterized by negative expression of the oncoprotein crbB2, positive p53, lack of VEGFR – C. Epstein–Barr virus-associated GC (EBVAGC was characterized by the absence of the VEGFR-C indicator protein and by the presence of crbB2 positive expression, in combination with a low, below 10 % expression, of the p53 oncoprotein. Conclusions. Understanding the nature of the GC various genetic variants makes possible two basic types of complex treatment individualization: the individualization of chemotherapy and the personification of the surgical modalities.

  4. Prenatal diagnosis and genetic counseling for Waardenburg syndrome type I and II in Chinese families

    Science.gov (United States)

    Wang, Li; Qin, Litao; Li, Tao; Liu, Hongjian; Ma, Lingcao; Li, Wan; Wu, Dong; Wang, Hongdan; Guo, Qiannan; Guo, Liangjie; Liao, Shixiu

    2018-01-01

    Waardenburg syndrome (WS) is an auditory-pigmentary disorder with varying combinations of sensorineural hearing loss and abnormal pigmentation. The present study aimed to investigate the underlying molecular pathology and provide a method of prenatal diagnosis of WS in Chinese families. A total of 11 patients with WS from five unrelated Chinese families were enrolled. A thorough clinical examination was performed on all participants. Furthermore, patients with WS underwent screening for mutations in the following genes: Paired box 3 (PAX3), melanogenesis associated transcription factor (MITF), SRY-box 10, snail family transcriptional repressor 2 and endothelin receptor type B using polymerase chain reaction sequencing. Array-based comparative genomic hybridization was used for specific patients whose sequence results were normal. Following identification of the genotype of the probands and their parents, prenatal genetic diagnosis was performed for family 01 and 05. According to the diagnostic criteria for WS, five cases were diagnosed as WS1, while the other six cases were WS2. Genetic analysis revealed three mutations, including a nonsense mutation PAX3 c.583C>T in family 01, a splice-site mutation MITF c.909G>A in family 03 and an in-frame deletion MITF c.649_651delGAA in family 05. To the best of the authors' knowledge the mutations (c.583C>T in PAX3 and c.909G>A in MITF) were reported for the first time in Chinese people. Mutations in the gene of interest were not identified in family 02 and 04. The prenatal genetic testing of the two fetuses was carried out and demonstrated that the two babies were normal. The results of the present study expanded the range of known genetic mutations in China. Identification of genetic mutations in these families provided an efficient way to understand the causes of WS and improved genetic counseling. PMID:29115496

  5. Prevalence of Metabolic Syndrome and its influence on microvascular complications in the Indian population with Type 2 Diabetes Mellitus. Sankara Nethralaya Diabetic Retinopathy Epidemiology And Molecular Genetic Study (SN-DREAMS, report 14

    Directory of Open Access Journals (Sweden)

    Raman Rajiv

    2010-11-01

    Full Text Available Abstract Background The Metabolic syndrome (MS consists of central obesity, glucose intolerance, hyperinsulinemia, low high density lipoproteins, high triglycerides and hypertension. Different studies have observed that MS causes microvascular complications in patients with type 2 diabetes. The aim of the study was to find out the prevalence of MS in the Indian population with type 2 diabetes mellitus in relation to gender, duration of diabetes, and to evaluate the influence of MS and its individual components on microvascular complications such as diabetic retinopathy, diabetic nephropathy and diabetic neuropathy. Methods A population-based cross sectional survey was conducted with 1414 patients having type 2 diabetes mellitus. The International Diabetes Federation (IDF criteria were used to identify the metabolic syndrome. Diabetic retinopathy was graded using the stereoscopic digital fundus photography. Neuropathy was assessed by measuring the vibration perception threshold through a sensitometer. Nephropathy was diagnosed by the presence of microalbuminuria in the first morning urine sample. Results The age and gender adjusted prevalence of MS, using the IDF criteria, in the South Indian population was 73.3%. The prevalence was higher in women (83.3%, compared to men (65.3%. In subjects with diabetes mellitus, without and with MS, the prevalence of retinopathy was 21.3% and 16.9% (p = 0.057; prevalence of nephropathy was 20.5% and 18.0% (p = 0.296, and prevalence of neuropathy was17.2% and 19.4% (p = 0.353 respectively. Overall and in women, the clustering of MS components led to an increase in the prevalence of diabetic nephropathy. The prevalence of retinopathy and neuropathy in MS subjects, who had diabetes for Conclusions The association of MS with microangiopathies decreased with an increase in the duration of diabetes. MS behaved differently in men and women. It may need to be managed differently in the two groups.

  6. Molecular and genetic aspects of odontogenic tumors: a review.

    Science.gov (United States)

    Garg, Kavita; Chandra, Shaleen; Raj, Vineet; Fareed, Wamiq; Zafar, Muhammad

    2015-06-01

    Odontogenic tumors contain a heterogeneous collection of lesions that are categorized from hamartomas to benign and malignant neoplasms of inconstant aggressiveness. Odontogenic tumors are usually extraordinary with assessed frequency of short of 0.5 cases/100,000 population for every year. The lesions such as odontogenic tumors are inferred from the components of the tooth-structuring contraption. They are discovered solely inside the maxillary and mandibular bones. This audit speaks to experiences and cooperation of the molecular and genetic variations connected to the development and movement of odontogenic tumors which incorporate oncogenes, tumor-silencer genes, APC gene, retinoblastoma genes, DNA repair genes, onco-viruses, development components, telomerase, cell cycle controllers, apoptosis-related elements, and regulators/conttrollers of tooth development. The reasonable and better understanding of the molecular components may prompt new ideas for their detection and administrating a better prognosis of odontogenic tumors.

  7. Molecular and genetic aspects of odontogenic tumors: a review

    Directory of Open Access Journals (Sweden)

    Kavita Garg

    2015-06-01

    Full Text Available Odontogenic tumors contain a heterogeneous collection of lesions that are categorized from hamartomas to benign and malignant neoplasms of inconstant aggressiveness. Odontogenic tumors are usually extraordinary with assessed frequency of short of 0.5 cases/100,000 population for every year. The lesions such as odontogenic tumors are inferred from the components of the tooth-structuring contraption. They are discovered solely inside the maxillary and mandibular bones. This audit speaks to experiences and cooperation of the molecular and genetic variations connected to the development and movement of odontogenic tumors which incorporate oncogenes, tumor-silencer genes, APC gene, retinoblastoma genes, DNA repair genes, onco-viruses, development components, telomerase, cell cycle controllers, apoptosis-related elements, and regulators/controllers of tooth development. The reasonable and better understanding of the molecular components may prompt new ideas for their detection and administrating a better prognosis of odontogenic tumors.

  8. Testicular germ cell tumors: Molecular genetic and clinicomorphological aspects

    Directory of Open Access Journals (Sweden)

    M. V. Nemtsova

    2015-03-01

    Full Text Available Testicular tumors are the most common form of solid cancer in young men. According to the 2004 WHO classification, testicular germ cell tumors (TGCT may present with different histological types. Embryonic cells of varying grade may be a source of TGCT and the occurrence of this type of tumors is directly related to the formation of a pool of male sex cells and gametogenesis. The paper gives information on mo- lecular stages for the process of formation of male sex cells in health, as well as ways of their impairments leading to TGCT. An investigation of the profiles of gene expression and the spectrum of molecular damages revealed genes responsible for a predisposition to the sporadic and hereditary forms of TGCT. The paper presents the current molecular genetic and clinicomorphological characteristics of TGCT. 

  9. Genetics Home Reference: action myoclonus-renal failure syndrome

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    ... Conditions Action myoclonus–renal failure syndrome Action myoclonus–renal failure syndrome Printable PDF Open All Close All Enable ... view the expand/collapse boxes. Description Action myoclonus–renal failure (AMRF) syndrome causes episodes of involuntary muscle jerking ...

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    ... my area? Other Names for This Condition CISS CNTF receptor-related disorders Crisponi syndrome Sohar-Crisponi syndrome ... of cardiotrophin-like cytokine, a second ligand for ciliary neurotrophic factor receptor, leads to cold-induced sweating syndrome in ...

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    ... blepharophimosis-mental retardation syndrome, Maat-Kievit-Brunner type BMRS, MKB type Ohdo syndrome, MKB type X-linked ... D, Brunner H, Bitoun P. Blepharophimosis-mental retardation (BMR) syndromes: A proposed clinical classification of the so- ...

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    ... Home Health Conditions Deafness-dystonia-optic neuronopathy syndrome Deafness-dystonia-optic neuronopathy syndrome Printable PDF Open All ... Javascript to view the expand/collapse boxes. Description Deafness-dystonia-optic neuronopathy (DDON) syndrome, also known as ...

  13. Genetics Home Reference: Huntington disease-like syndrome

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    ... Twitter Home Health Conditions Huntington disease-like syndrome Huntington disease-like syndrome Printable PDF Open All Close ... collapse boxes. Description As its name suggests, a Huntington disease -like (HDL) syndrome is a condition that ...

  14. Genetics Home Reference: distal 18q deletion syndrome

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    ... Health Conditions Distal 18q deletion syndrome Distal 18q deletion syndrome Printable PDF Open All Close All Enable ... view the expand/collapse boxes. Description Distal 18q deletion syndrome is a chromosomal condition that occurs when ...

  15. Genetics Home Reference: proximal 18q deletion syndrome

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    ... Health Conditions Proximal 18q deletion syndrome Proximal 18q deletion syndrome Printable PDF Open All Close All Enable ... view the expand/collapse boxes. Description Proximal 18q deletion syndrome is a chromosomal condition that occurs when ...

  16. Genetics Home Reference: cri-du-chat syndrome

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    ... Health Conditions Cri-du-chat syndrome Cri-du-chat syndrome Printable PDF Open All Close All Enable ... view the expand/collapse boxes. Description Cri-du-chat (cat's cry) syndrome, also known as 5p- (5p ...

  17. Genetics Home Reference: Allan-Herndon-Dudley syndrome

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    ... Twitter Home Health Conditions Allan-Herndon-Dudley syndrome Allan-Herndon-Dudley syndrome Printable PDF Open All Close ... Javascript to view the expand/collapse boxes. Description Allan-Herndon-Dudley syndrome is a rare disorder of ...

  18. Genetics Home Reference: type A insulin resistance syndrome

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    ... Conditions Type A insulin resistance syndrome Type A insulin resistance syndrome Printable PDF Open All Close All Enable ... as energy. In people with type A insulin resistance syndrome , insulin resistance impairs blood sugar regulation and ultimately leads ...

  19. Genetics Home Reference: hyperparathyroidism-jaw tumor syndrome

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    ... Twitter Home Health Conditions Hyperparathyroidism-jaw tumor syndrome Hyperparathyroidism-jaw tumor syndrome Printable PDF Open All Close ... Javascript to view the expand/collapse boxes. Description Hyperparathyroidism-jaw tumor syndrome is a condition characterized by ...

  20. Genetics Home Reference: thiamine-responsive megaloblastic anemia syndrome

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    ... Thiamine-responsive megaloblastic anemia syndrome Thiamine-responsive megaloblastic anemia syndrome Printable PDF Open All Close All Enable ... the expand/collapse boxes. Description Thiamine-responsive megaloblastic anemia syndrome is a rare condition characterized by hearing ...