Abstract:
BACKGROUND:Cerebral cavernous malformations (CCMs) are vascular malformations mostly located within the central nervous system. Most deleterious variants are loss of function mutations in one of the three CCM genes. These genes code for proteins that form a ternary cytosolic complex with CCM2 as a hub. Very few CCM2 missense variants have been shown to be deleterious by modifying the ternary CCM complex stability. OBJECTIVES:To investigate the causality of novel missense CCM2 variants detected in patients with CCM. METHODS:The three CCM genes were screened in 984 patients referred for CCM molecular screening. Interaction between CCM1 and CCM2 proteins was tested using co-immunoprecipitation experiments for the CCM2 missense variants located in the phosphotyrosine binding (PTB) domain. RESULTS:11 distinct CCM2 rare missense variants were found. Six variants predicted to be damaging were located in the PTB domain, four of them were novel. When co-transfected with CCM1 in HEK293T cells, a loss of interaction between CCM1 and CCM2 was observed for all six variants. CONCLUSION:We showed, using co-immunoprecipitation experiments, that CCM2 missense variants located in the PTB domain were actually damaging by preventing the normal interaction between CCM1 and CCM2. These data are important for diagnosis and genetic counselling, which are challenging in patients harbouring such variants.
journal_name
J Med Genetjournal_title
Journal of medical geneticsauthors
Bergametti F,Viot G,Verny C,Brechard MP,Denier C,Labauge P,Petit P,Nouet A,Viallet F,Chaussenot A,Hervé D,Tournier-Lasserve E,Riant Fdoi
10.1136/jmedgenet-2019-106401subject
Has Abstractpub_date
2020-06-01 00:00:00pages
400-404issue
6eissn
0022-2593issn
1468-6244pii
jmedgenet-2019-106401journal_volume
57pub_type
杂志文章abstract:BACKGROUND:Members of two seemingly unrelated kindreds of Arab Moslem origin presented with pronounced early onset spastic paraparesis of upper and lower limbs, mild intellectual disability, kyphosis, pectus carinatum and hypertrichosis. METHODS:The authors performed neurological and developmental examinations on the ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmedgenet-2012-100742
更新日期:2012-07-01 00:00:00
abstract:BACKGROUND:Limb-girdle muscular dystrophy type R1 (LGMDR1) can be caused by recessive CAPN3 mutations accounting for the majority of LGMD. To date, no systemic evaluation has been performed to analyse the detrimental and normal mutations on CAPN3 and its hotspots. METHODS:CAPN3 variants (n=112) from a total of 124 pat...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmedgenet-2020-107159
更新日期:2020-09-29 00:00:00
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
更新日期:2000-11-01 00:00:00
abstract:BACKGROUND:The apolipoprotein E (ApoE) polymorphism has been well studied in the adult human population, in part because the e4 allele is a known risk factor for Alzheimer's disease. Little is known of the distribution of ApoE alleles in newborns, and their association with perinatal brain damage has not been investiga...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.2005.033936
更新日期:2006-05-01 00:00:00
abstract::We have performed linkage analysis in seven Italian families, in which mild osteogenesis imperfecta (OI) segregated as a dominant trait, by means of six DNA restriction fragment length polymorphisms (RFLPs) of type I collagen genes. OI type I was linked to the alpha 1(I) gene (COL1A1) in two families, and to the alpha...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.27.6.367
更新日期:1990-06-01 00:00:00
abstract:BACKGROUND:Lysosomal protein profiling is being developed as a high throughput method to screen populations for lysosomal storage disorders (LSD). DESIGN:1415 blood spots from patients referred to a metabolic clinic for LSD were screened using a single multiplex assay for 14 proteins in a dried blood spot. RESULTS:Al...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.2010.088096
更新日期:2011-06-01 00:00:00
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journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.21.2.114
更新日期:1984-04-01 00:00:00
abstract::Pericentric inversions in chromosome 2 were traced in 2 unrelated North American black families. In the case of inv(2)(p13q11) no effect on reproduction was observed. In the case of inv(2)(p11q13) some reproductive abnormalities were noted which might be related to the inversion. ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.15.5.388
更新日期:1978-10-01 00:00:00
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journal_title:Journal of medical genetics
pub_type: 杂志文章
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更新日期:2013-07-01 00:00:00
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journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:
更新日期:1999-04-01 00:00:00
abstract::Spinocerebellar ataxia type 2 (SCA2) is caused by the expansion of an unstable CAG repeat encoding a polyglutamine tract. Repeats with 32 to 200 CAGs are associated with the disease, whereas normal chromosomes contain 13 to 33 repeats. We tested 220 families of different geographical origins for the SCA2 mutation. Thi...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:
更新日期:1999-05-01 00:00:00
abstract::A 6-year-old boy with speech delay and mild mental retardation (IQ 82) was found to have a complex double translocation involving four chromosomes and a total of five breakpoints, two being on the same arm. This resulted in the karyotype 46,XY,t(2;4;7)(7;8)(q14;q31;q11q22;q13). As far as the authors are aware this is ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.20.5.389
更新日期:1983-10-01 00:00:00
abstract:BACKGROUND:The extent which universally common or population-specific alleles can explain between-population variations in phenotypes is unknown. The heritable coronary heart disease risk factor lipoprotein(a) (Lp(a)) level provides a useful case study of between-population variation, as the aetiology of twofold higher...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.2006.042119
更新日期:2006-12-01 00:00:00
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journal_title:Journal of medical genetics
pub_type: 杂志文章,评审
doi:10.1136/jmg.25.6.377
更新日期:1988-06-01 00:00:00
abstract::Chromosome 1 is thought to represent about 6% of the total human genome and the 85 loci so far identified may constitute about 1% of the genes present on this chromosome. The existence of at least 22 loci sufficiently polymorphic in Europeans to be useful as genetic markers has allowed the construction of an elementar...
journal_title:Journal of medical genetics
pub_type: 杂志文章,评审
doi:10.1136/jmg.23.2.107
更新日期:1986-04-01 00:00:00
abstract::We describe 14 boys and six girls, including monozygotic twins, with the CHARGE association. All of the children had at least four of the seven major features included in the mnemonic CHARGE and all had ear anomalies or deafness or both and either coloboma or choanal atresia or both. All the boys had evidence of hypog...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.25.3.147
更新日期:1988-03-01 00:00:00
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journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.28.6.402
更新日期:1991-06-01 00:00:00
abstract::We present an extended family with Li-Fraumeni syndrome characterised by gastric and breast carcinoma, glioma, sarcoma, and leukaemia. This family showed strong evidence of linkage to TP53, and three of four tumours analysed showed loss of the wild type allele. A codon 175 missense mutation was identified in exon 5 in...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.32.12.942
更新日期:1995-12-01 00:00:00
abstract::Abnormalities of dystrophin, the sarcoglycans, and laminin alpha2 are responsible for a subset of the muscular dystrophies. In this study we aim to characterise the nature and frequency of abnormalities of these proteins in an Australian population and to formulate an investigative algorithm to aid in approaching the ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
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更新日期:1998-05-01 00:00:00
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journal_title:Journal of medical genetics
pub_type: 杂志文章
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journal_title:Journal of medical genetics
pub_type: 杂志文章
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journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmedgenet-2013-101680
更新日期:2013-11-01 00:00:00
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journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.10.2.144
更新日期:1973-06-01 00:00:00
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journal_title:Journal of medical genetics
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doi:10.1136/jmg.34.2.133
更新日期:1997-02-01 00:00:00
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journal_title:Journal of medical genetics
pub_type: 信件
doi:10.1136/jmg.2005.035667
更新日期:2006-06-01 00:00:00
abstract::A new case of trisomy 19q13.2-->qter is described in a male child which was caused by a maternal balanced translocation (13;19)(p13;q13.2). The major clinical features detected in the patient included the following: facial dysmorphism, bilateral coloboma, narrow and hypoplastic nails, cardiac malformations (Fallot's t...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.30.8.697
更新日期:1993-08-01 00:00:00
abstract::Our primary objective was to estimate, by one year and five year intervals, maternal age specific risk rates for Down syndrome among whites and among other races from two different populations, metropolitan Atlanta and south west Ohio, using live birth and prenatally diagnosed cases ascertained during 1970-1989. The f...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.35.6.482
更新日期:1998-06-01 00:00:00
abstract::Autism spectrum disorders represent a group of developmental disorders with strong genetic underpinnings. Several cytogenetic abnormalities or de novo mutations able to cause autism have recently been uncovered. In this study, the literature was reviewed to highlight genotype-phenotype correlations between causal gene...
journal_title:Journal of medical genetics
pub_type: 杂志文章,评审
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更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:The cohesin complex plays an essential role in genome organisation and cell division. A full complement of the cohesin complex and its regulators is important for normal development, since heterozygous mutations in genes encoding these components can be sufficient to produce a disease phenotype. The implicat...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmedgenet-2020-107095
更新日期:2020-09-11 00:00:00
abstract::We report on a boy with a maternal uniparental disomy for chromosome 14 (UPD(14)). At 7 years of age he was referred to us by the paediatrician because of symptoms of Prader-Willi syndrome (PWS). He showed short stature, obesity, mild developmental delay, cryptorchidism, and some mild dysmorphic features. The history ...
journal_title:Journal of medical genetics
pub_type: 杂志文章,评审
doi:10.1136/jmg.36.10.782
更新日期:1999-10-01 00:00:00