Exome sequencing identifies rare variants in multiple genes in atrioventricular septal defect.
Genet Med
; 18(2): 189-98, 2016 Feb.
Article
em En
| MEDLINE
| ID: mdl-25996639
ABSTRACT
PURPOSE:
The genetic etiology of atrioventricular septal defect (AVSD) is unknown in 40% cases. Conventional sequencing and arrays have identified the etiology in only a minority of nonsyndromic individuals with AVSD.METHODS:
Whole-exome sequencing was performed in 81 unrelated probands with AVSD to identify potentially causal variants in a comprehensive set of 112 genes with strong biological relevance to AVSD.RESULTS:
A significant enrichment of rare and rare damaging variants was identified in the gene set, compared with controls (odds ratio (OR) 1.52; 95% confidence interval (CI) 1.35-1.71; P = 4.8 × 10(-11)). The enrichment was specific to AVSD probands, compared with a cohort without AVSD with tetralogy of Fallot (OR 2.25; 95% CI 1.84-2.76; P = 2.2 × 10(-16)). Six genes (NIPBL, CHD7, CEP152, BMPR1a, ZFPM2, and MDM4) were enriched for rare variants in AVSD compared with controls, including three syndrome-associated genes (NIPBL, CHD7, and CEP152). The findings were confirmed in a replication cohort of 81 AVSD probands.CONCLUSION:
Mutations in genes with strong biological relevance to AVSD, including syndrome-associated genes, can contribute to AVSD, even in those with isolated heart disease. The identification of a gene set associated with AVSD will facilitate targeted genetic screening in this cohort.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Variação Genética
/
Exoma
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Defeitos dos Septos Cardíacos
Tipo de estudo:
Etiology_studies
/
Incidence_studies
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Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limite:
Adolescent
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Female
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Humans
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Male
Idioma:
En
Revista:
Genet Med
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Canadá