当前位置： SCI文献检索 > JOURNAL OF MEDICAL GENETICS期刊下所有文献 > Homozygous hypomorphic BRCA2 variant in primary ovarian insufficiency without cancer or Fanconi anaemia trait.

Homozygous hypomorphic BRCA2 variant in primary ovarian insufficiency without cancer or Fanconi anaemia trait.

Abstract：

BACKGROUND:Primary ovarian insufficiency (POI) affects 1% of women under 40 years and is a public health problem. The genetic causes of POI are highly heterogeneous with isolated or syndromic forms. Recently, variants in genes involved in DNA repair have been shown to cause POI. Notably, syndromic POI with Fanconi anaemia (FA) traits related to biallelic BRCA2 truncated variants has been reported. Here, we report a novel phenotype of isolated POI with a BRCA2 variant in a consanguineous Turkish family. METHODS:Exome sequencing (ES) was performed in the patient. We also performed functional studies, including a homologous recombination (HR) test, cell proliferation, radiation-induced RAD51 foci formation assays and chromosome breakage studies in primary and lymphoblastoid immortalised cells. The expression of BRCA2 in human foetal ovaries was studied. RESULTS:ES identified a homozygous missense c.8524C>T/p.R2842C-BRCA2 variant. BRCA2 defects induce cancer predisposition and FA. Remarkably, neither the patient nor her family exhibited somatic pathologies. The patient's cells showed intermediate levels of chromosomal breaks, cell proliferation and radiation-induced RAD51 foci formation compared with controls and FA cells. R2842C-BRCA2 only partially complemented HR efficiency compared with wild type-BRCA2. BRCA2 is expressed in human foetal ovaries in pachytene stage oocytes, when meiotic HR occurs. CONCLUSION:We describe the functional assessment of a homozygous hypomorphic BRCA2 variant in a patient with POI without cancer or FA trait. Our findings extend the phenotype of BRCA2 biallelic alterations to fully isolated POI. This study has a major impact on the management and genetic counselling of patients with POI.

journal_name

J Med Genet

journal_title

Journal of medical genetics

authors

Caburet S,Heddar A,Dardillac E,Creux H,Lambert M,Messiaen S,Tourpin S,Livera G,Lopez BS,Misrahi M

doi

10.1136/jmedgenet-2019-106672

subject

Has Abstract

pub_date

2020-06-01 00:00:00

eissn

0022-2593

issn

1468-6244

pii

jmedgenet-2019-106672

pub_type

杂志文章

相关文献

JOURNAL OF MEDICAL GENETICS文献大全
  • Extra G positive band on the long arm of chromosome 9.

    abstract：:Various heteromorphisms of the 9q heterochromatic area have been reported. In most instances, the extra G positive band is accompanied by an extra C band. We describe a family where the extra G band is totally euchromatic and does not include an extra C band. It is not clear whether these two types of variant chromoso...

    journal_title：Journal of medical genetics

    pub_type： 杂志文章

    doi：10.1136/jmg.30.7.613

    authors： Knight LA,Soon GM,Tan M

    更新日期：1993-07-01 00:00:00

  • Interstitial deletion in the long arms of chromosome 1: 46,XY,del(1)(pter leads to q22::q25 leads to qter).

    abstract：:A child was brought to us with multiple anomalies. On examination we found an interstitial deletion in the long arms of chromosome 1. We studied genetic and chromosome markers, comparing our clinical and cytogenetic findings with other reported cases of chromosome 1 interstitial deletion. ...

    journal_title：Journal of medical genetics

    pub_type： 杂志文章

    doi：10.1136/jmg.17.6.483

    authors： de Pablo CE,García Sagredo JM,Ferro MT,Ferrando P,San Román C

    更新日期：1980-12-01 00:00:00

  • Molecular, cytogenetic, and clinical characterisation of six XX males including one prenatal diagnosis.

    abstract：:Cytogenetic analysis, fluorescent in situ hybridisation (FISH), and molecular amplification have been used to characterise the transfer of Yp fragments to Xp22.3 in six XX males. PCR amplification of the genes SRY, RPS4Y, ZFY, AMELY, KALY, and DAZ and of several other markers along the Y chromosome short and long arms...

    journal_title：Journal of medical genetics

    pub_type： 杂志文章

    doi：10.1136/jmg.35.9.727

    authors： Margarit E,Soler A,Carrió A,Oliva R,Costa D,Vendrell T,Rosell J,Ballesta F

    更新日期：1998-09-01 00:00:00

  • A novel APC mutation defines a second locus for Cenani-Lenz syndrome.

    abstract：BACKGROUND:Cenani-Lenz syndrome (CLS) is an autosomal recessive condition characterised by a unique pattern of syndactyly, and variable penetrance of renal agenesis and facial dysmorphism. LRP4 mutations were identified in most, but not all patients with this syndrome, suggesting the presence of at least one additional...

    journal_title：Journal of medical genetics

    pub_type： 杂志文章

    doi：10.1136/jmedgenet-2014-102850

    authors： Patel N,Faqeih E,Anazi S,Alfawareh M,Wakil SM,Colak D,Alkuraya FS

    更新日期：2015-05-01 00:00:00

  • Spatial relationship of human X and Y chromosomes at somatic metaphase.

    abstract：:A total of 592 cells was examined from 38 normal humans who had either small or very large Y chromosomes. Chromosome identification was based on the QFQ technique. The distance between the X and Y chromosome was measured from centromere to centromere. The spatial distance between X and Y was significantly smaller when...

    journal_title：Journal of medical genetics

    pub_type： 杂志文章

    doi：10.1136/jmg.20.6.450

    authors： Dosik D,Verma RS

    更新日期：1983-12-01 00:00:00

  • A novel microdeletion syndrome at 3q13.31 characterised by developmental delay, postnatal overgrowth, hypoplastic male genitals, and characteristic facial features.

    abstract：BACKGROUND:Congenital deletions affecting 3q11q23 have rarely been reported and only five cases have been molecularly characterised. Genotype-phenotype correlation has been hampered by the variable sizes and breakpoints of the deletions. In this study, 14 novel patients with deletions in 3q11q23 were investigated and c...

    journal_title：Journal of medical genetics

    pub_type： 杂志文章

    doi：10.1136/jmedgenet-2011-100534

    authors： Molin AM,Andrieux J,Koolen DA,Malan V,Carella M,Colleaux L,Cormier-Daire V,David A,de Leeuw N,Delobel B,Duban-Bedu B,Fischetto R,Flinter F,Kjaergaard S,Kok F,Krepischi AC,Le Caignec C,Ogilvie CM,Maia S,Mathieu-Drama

    更新日期：2012-02-01 00:00:00

  • Unilateral radial aplasia and trisomy 22 mosaicism.

    abstract：:A child with unilateral radial aplasia, asymmetry, other malformations, and severe physical and mental retardation is reported. In blood and bone marrow cultures a low mosaicism for trisomy 22 was found. In a few cells a chromosome 22 was missing. The importance of early cytogenetic analysis on large numbers of cells ...

    journal_title：Journal of medical genetics

    pub_type： 杂志文章

    doi：10.1136/jmg.18.6.473

    authors： Dulitzky F,Shabtal F,Zlotogora J,Halbrecht I,Elian E

    更新日期：1981-12-01 00:00:00

  • A liminal stage after predictive testing for Huntington disease.

    abstract：BACKGROUND:Following predictive testing for Huntington disease (HD), knowledge of one's carrier status may have consequences on disease onset. Our study aimed to address two questions. First, does knowledge of being a carrier of the pathological HD mutation trigger onset of the disease? Second, does this knowledge infl...

    journal_title：Journal of medical genetics

    pub_type： 杂志文章

    doi：10.1136/jmedgenet-2016-104199

    authors： Gargiulo M,Tezenas du Montcel S,Jutras MF,Herson A,Cazeneuve C,Durr A

    更新日期：2017-08-01 00:00:00

  • Extravillus dividing fetal cells at CVS: evidence of their erythroblastic origin.

    abstract：:Cytological and cytogenetic studies were performed on nucleated fetal cells present in chorionic villus transport medium. The erythroblastic origin of these cells was shown. Fetal erythroblasts in spontaneous mitosis were frequently observed; chromosome counts were obtained from them but poor quality often prevented b...

    journal_title：Journal of medical genetics

    pub_type： 杂志文章

    doi：10.1136/jmg.29.10.709

    authors： Terzoli G,Cartolano R,Rossella F,Cantù-Rajnoldi A,Brambati B,Fraccaro M,Simoni G

    更新日期：1992-10-01 00:00:00

  • Porencephalic cyst in pycnodysostosis.

    abstract：:We describe a case of pycnodysostosis with porencephaly and suggest an explanation for the porencephaly by a mechanism of imbalance between brain growth and its vascular supply and a normal but unopposed cerebrospinal fluid pressure. ...

    journal_title：Journal of medical genetics

    pub_type： 杂志文章

    doi：10.1136/jmg.26.12.782

    authors： Figueiredo J,Reis A,Vaz R,Leáo M,Cruz C

    更新日期：1989-12-01 00:00:00

  • An interstitial deletion of 6p24-p25 proximal to the FKHL7 locus and including AP-2alpha that affects anterior eye chamber development.

    abstract：:The FKHL7 gene has been implicated in the pathogenesis of glaucoma/autosomal dominant iridogoniodysgenesis (IGDA) (IRID1). This has been supported by mutations in some glaucoma and IGDA patients and the development of anterior eye chamber anomalies in patients with 6p deletions affecting the 6p25 region. We report a c...

    journal_title：Journal of medical genetics

    pub_type： 杂志文章

    doi：

    authors： Davies AF,Mirza G,Flinter F,Ragoussis J

    更新日期：1999-09-01 00:00:00

  • Matrilin-3 mutations that cause chondrodysplasias interfere with protein trafficking while a mutation associated with hand osteoarthritis does not.

    abstract：:Several mutations in the extracellular matrix protein matrilin-3 cause a heterogeneous disease spectrum affecting skeletal tissues. We introduced three disease causing point mutations leading to single amino acid exchanges (R116W, T298M, C299S) in matrilin-3 and expressed the corresponding proteins in primary articula...

    journal_title：Journal of medical genetics

    pub_type： 杂志文章

    doi：10.1136/jmg.2004.029462

    authors： Otten C,Wagener R,Paulsson M,Zaucke F

    更新日期：2005-10-01 00:00:00

  • Six-year prospective follow-up study in 151 carriers of the mitochondrial DNA 3243 A>G variant.

    abstract：BACKGROUND:The mitochondrial DNA (mDNA) 3243A>G variant is the most common pathogenic variant of the mDNA. To interpret results of clinical trials in mitochondrial disease, it is important to have a clear understanding of the natural course of disease. To obtain more insight into the disease burden and the progression ...

    journal_title：Journal of medical genetics

    pub_type： 杂志文章

    doi：10.1136/jmedgenet-2019-106800

    authors： de Laat P,Rodenburg RR,Roeleveld N,Koene S,Smeitink JA,Janssen MC

    更新日期：2021-01-01 00:00:00

  • Disease associated balanced chromosome rearrangements: a resource for large scale genotype-phenotype delineation in man.

    abstract：:Disease associated balanced chromosomal rearrangements (DBCRs), which truncate, delete, or otherwise inactivate specific genes, have been instrumental for positional cloning of many disease genes. A network of cytogenetic laboratories, Mendelian Cytogenetics Network (MCN), has been established to facilitate the identi...

    journal_title：Journal of medical genetics

    pub_type： 杂志文章

    doi：10.1136/jmg.37.11.858

    authors： Bugge M,Bruun-Petersen G,Brøndum-Nielsen K,Friedrich U,Hansen J,Jensen G,Jensen PK,Kristoffersson U,Lundsteen C,Niebuhr E,Rasmussen KR,Rasmussen K,Tommerup N

    更新日期：2000-11-01 00:00:00

  • Trisomy 18 syndrome with an unusual karyotype: possible double isochromosome.

    abstract：:Chromosome analysis of an infant with characteristic features of trisomy 18 is presented. The chromosome complement contained a modal count of 47 but there was only one No. 18. In addition, there were two metacentric chromosomes of different sizes. The two metacentric chromosomes were identified by G- and C-banding to...

    journal_title：Journal of medical genetics

    pub_type： 杂志文章

    doi：10.1136/jmg.15.1.73

    authors： Larson LM,Wasdahl WA,Saumur JH,Coleman ML,Jalal SM

    更新日期：1978-02-01 00:00:00

  • Absence of BRAF mutations in UV-protected mucosal melanomas.

    abstract：BACKGROUND:Mutations in BRAF have recently been identified in a significant percentage of primary and metastatic cutaneous malignant melanomas. As ultraviolet (UV) exposure may play a role in the development of cutaneous melanoma lesions with BRAF mutations, BRAF mutation frequency in melanomas arising in sites protect...

    journal_title：Journal of medical genetics

    pub_type： 杂志文章

    doi：10.1136/jmg.2003.016667

    authors： Edwards RH,Ward MR,Wu H,Medina CA,Brose MS,Volpe P,Nussen-Lee S,Haupt HM,Martin AM,Herlyn M,Lessin SR,Weber BL

    更新日期：2004-04-01 00:00:00

  • Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome.

    abstract：:Immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX, OMIM 304790) is a rare, recessive disorder resulting in aggressive autoimmunity and early death. Mutations in FOXP3 have been identified in 13 of 14 patients tested. Research in the mouse model, scurfy, suggests that autoimmunity may stem from a lac...

    journal_title：Journal of medical genetics

    pub_type： 杂志文章,评审

    doi：10.1136/jmg.39.8.537

    authors： Wildin RS,Smyk-Pearson S,Filipovich AH

    更新日期：2002-08-01 00:00:00

  • Mitochondrial mutation commonly associated with Leber's hereditary optic neuropathy observed in a patient with Wolfram syndrome (DIDMOAD).

    abstract：:DIDMOAD is usually considered an autosomal recessive condition, with wide phenotypic variation, but the possibility of mitochondrial mutations occurring in this condition has been considered. A 19 year old man presented with long standing diabetes mellitus, optic atrophy, and grand mal seizures. Further investigations...

    journal_title：Journal of medical genetics

    pub_type： 杂志文章,评审

    doi：10.1136/jmg.31.4.328

    authors： Pilz D,Quarrell OW,Jones EW

    更新日期：1994-04-01 00:00:00

  • Genome-wide association study of smoking behaviours among Bangladeshi adults.

    abstract：BACKGROUND:The high prevalence of tobacco use in some developing nations, including Bangladesh, poses several public health challenges for these populations. Smoking behaviour is determined by genetic and environmental factors; however, the genetic determinants of smoking behaviour have not been previously examined in ...

    journal_title：Journal of medical genetics

    pub_type： 杂志文章

    doi：10.1136/jmedgenet-2013-102151

    authors： Argos M,Tong L,Pierce BL,Rakibuz-Zaman M,Ahmed A,Islam T,Rahman M,Paul-Brutus R,Rahaman R,Roy S,Jasmine F,Kibriya MG,Ahsan H

    更新日期：2014-05-01 00:00:00

  • Neural tube defects: a survey of lesion descriptions made by different European pathologists.

    abstract：:Recent epidemiological interest has focused on separation of neural tube defects (NTD) into subgroups which may differ pathogenetically and aetiologically, for example, 'upper' and 'lower' spina bifida. In order to validate the use of pathologists' lesion descriptions by epidemiologists and others, a postal survey of ...

    journal_title：Journal of medical genetics

    pub_type： 杂志文章

    doi：10.1136/jmg.30.11.942

    authors： Dolk H,Seller MJ

    更新日期：1993-11-01 00:00:00

  • Prenatal diagnosis of osteogenesis imperfecta by identification of the concordant collagen 1 allele.

    abstract：:Dominantly inherited osteogenesis imperfecta is consistently linked to the two loci encoding the alpha 1 and alpha 2 subunits of collagen 1, the predominant bone collagen. We have performed several prenatal diagnoses based on identification of the segregating allele at the concordant locus in chorionic villus samples ...

    journal_title：Journal of medical genetics

    pub_type： 杂志文章

    doi：10.1136/jmg.28.3.145

    authors： Lynch JR,Ogilvie D,Priestley L,Baigrie C,Smith R,Farndon P,Sykes B

    更新日期：1991-03-01 00:00:00

  • Amelogenesis imperfecta in familial hypomagnesaemia and hypercalciuria with nephrocalcinosis caused by CLDN19 gene mutations.

    abstract：BACKGROUND:Amelogenesis imperfecta (AI) is a group of genetic diseases characterised by tooth enamel defects. AI was recently described in patients with familial hypercalciuria and hypomagnesaemia with nephrocalcinosis (FHHNC) caused by CLDN16 mutations. In the kidney, claudin-16 interacts with claudin-19 to control th...

    journal_title：Journal of medical genetics

    pub_type： 杂志文章

    doi：10.1136/jmedgenet-2016-103956

    authors： Yamaguti PM,Neves FA,Hotton D,Bardet C,de La Dure-Molla M,Castro LC,Scher MD,Barbosa ME,Ditsch C,Fricain JC,de La Faille R,Figueres ML,Vargas-Poussou R,Houillier P,Chaussain C,Babajko S,Berdal A,Acevedo AC

    更新日期：2017-01-01 00:00:00

  • Novel KIF7 mutations extend the phenotypic spectrum of acrocallosal syndrome.

    abstract：BACKGROUND:Acrocallosal syndrome (ACLS) is a rare recessive disorder characterised by corpus callosum agenesis or hypoplasia, craniofacial dysmorphism, duplication of the hallux, postaxial polydactyly, and severe mental retardation. Recently, we identified mutations in KIF7, a key component of the Sonic hedgehog pathwa...

    journal_title：Journal of medical genetics

    pub_type： 杂志文章

    doi：10.1136/jmedgenet-2012-101016

    authors： Putoux A,Nampoothiri S,Laurent N,Cormier-Daire V,Beales PL,Schinzel A,Bartholdi D,Alby C,Thomas S,Elkhartoufi N,Ichkou A,Litzler J,Munnich A,Encha-Razavi F,Kannan R,Faivre L,Boddaert N,Rauch A,Vekemans M,Attié-Bitac

    更新日期：2012-11-01 00:00:00

  • Genetic landscape of interactive effects of HLA-DRB1 alleles on susceptibility to ACPA(+) rheumatoid arthritis and ACPA levels in Japanese population.

    abstract：BACKGROUND:HLA-DRB1 is the strongest susceptibility gene to rheumatoid arthritis (RA). HLA-DRB1 alleles showed significant non-additive and interactive effects on susceptibility to RA in the European population, but these effects on RA susceptibility should vary between populations due to the difference in allelic dist...

    journal_title：Journal of medical genetics

    pub_type： 杂志文章

    doi：10.1136/jmedgenet-2017-104779

    authors： Terao C,Okada Y,Ikari K,Kochi Y,Suzuki A,Ohmura K,Matsuo K,Taniguchi A,Kubo M,Raychaudhuri S,Yamamoto K,Yamanaka H,Kamatani Y,Mimori T,Matsuda F

    更新日期：2017-12-01 00:00:00

  • Evidence of genetic heterogeneity in the autosomal recessive adult forms of limb-girdle muscular dystrophy following linkage analysis with 15q probes in Brazilian families.

    abstract：:The autosomal recessive limb-girdle muscular dystrophies (LGMD) represent a heterogeneous group of diseases which may be characterised by one or more autosomal loci. A gene at 15q has recently been found to be responsible for a mild form of LGMD in a group of families from the isolated island of Réunion, now classifie...

    journal_title：Journal of medical genetics

    pub_type： 杂志文章

    doi：10.1136/jmg.30.5.385

    authors： Passos-Bueno MR,Richard I,Vainzof M,Fougerousse F,Weissenbach J,Broux O,Cohen D,Akiyama J,Marie SK,Carvalho AA

    更新日期：1993-05-01 00:00:00

  • Genomic imprinting: a possible mechanism for the parental origin effect in Huntington's chorea.

    abstract：:Huntington's disease (HD) is an autosomal dominant condition with almost complete penetrance. The age of onset of the symptoms, however, is variable and depends on the parental origin of the gene. A high proportion of early onset cases inherit the HD gene from their father, whereas a considerable proportion of late on...

    journal_title：Journal of medical genetics

    pub_type： 杂志文章

    doi：10.1136/jmg.25.12.805

    authors： Reik W

    更新日期：1988-12-01 00:00:00

  • Evidence of digenic inheritance in Alport syndrome.

    abstract：BACKGROUND:Alport syndrome is a clinically heterogeneous, progressive nephropathy caused by mutations in collagen IV genes, namely COL4A3 and COL4A4 on chromosome 2 and COL4A5 on chromosome X. The wide phenotypic variability and the presence of incomplete penetrance suggest that a simple Mendelian model cannot complete...

    journal_title：Journal of medical genetics

    pub_type： 杂志文章

    doi：10.1136/jmedgenet-2014-102822

    authors： Mencarelli MA,Heidet L,Storey H,van Geel M,Knebelmann B,Fallerini C,Miglietti N,Antonucci MF,Cetta F,Sayer JA,van den Wijngaard A,Yau S,Mari F,Bruttini M,Ariani F,Dahan K,Smeets B,Antignac C,Flinter F,Renieri A

    更新日期：2015-03-01 00:00:00

  • Severe developmental delay and multiple strawberry naevi: a new syndrome?

    abstract：:An 18 month old girl with dysmorphic features, severe developmental delay, multiple strawberry naevi, and capillary naevi is described. No previous report of a similar association of features has been identified. ...

    journal_title：Journal of medical genetics

    pub_type： 杂志文章

    doi：10.1136/jmg.30.10.883

    authors： Upton CJ,Young ID

    更新日期：1993-10-01 00:00:00

  • Mitochondrial DNA haplogroups and type 2 diabetes: a study of 897 cases and 1010 controls.

    abstract：:Mitochondria play a central role in the secretion of insulin by pancreatic beta-cells, and pathogenic mutations of mitochondrial DNA (mtDNA) can cause diabetes. The aetiology of type 2 diabetes has a strong genetic component, raising the possibility that genetic variants of mtDNA alter the risk of developing the disor...

    journal_title：Journal of medical genetics

    pub_type： 杂志文章

    doi：10.1136/jmg.2007.048876

    authors： Chinnery PF,Mowbray C,Patel SK,Elson JL,Sampson M,Hitman GA,McCarthy MI,Hattersley AT,Walker M

    更新日期：2007-06-01 00:00:00

  • De novo 1;10 balanced translocation in an infant with thanatophoric dysplasia: a clue to the locus of the candidate gene.

    abstract：:A female infant with thanatophoric dysplasia was found to have a de novo translocation involving chromosomes 1 and 10. The chromosome abnormality may represent an important clue in identifying the locus for the candidate gene responsible for this lethal skeletal dysplasia. ...

    journal_title：Journal of medical genetics

    pub_type： 杂志文章

    doi：10.1136/jmg.32.4.293

    authors： Hersh JH,Yen FF,Peiper SC,Barch MJ,Yacoub OA,Voss DH,Roberts JL

    更新日期：1995-04-01 00:00:00