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The diagnostic value of next generation sequencing in familial nonsyndromic congenital heart defects
Author(s) -
Jia Yaojuan,
Louw Jacoba J.,
Breckpot Jeroen,
Callewaert Bert,
Barrea Catherine,
Sznajer Yves,
Gewillig Marc,
Souche Erika,
Dehaspe Luc,
Vermeesch Joris Robert,
Lambrechts Diether,
Devriendt Koenraad,
Corveleyn Anniek
Publication year - 2015
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.37108
Subject(s) - value (mathematics) , medicine , dna sequencing , genetics , computer science , biology , gene , machine learning
To determine the diagnostic value of massive parallel sequencing of a panel of known cardiac genes in familial nonsyndromic congenital heart defects (CHD), targeted sequencing of the coding regions of 57 genes previously implicated in CHD was performed in 36 patients from 13 nonsyndromic CHD families with probable autosomal dominant inheritance. Following variant analysis and Sanger validation, we identified six potential disease causing variants in three genes ( MYH6, NOTCH1 , and TBX5 ), which may explain the defects in six families. Several problematic situations were encountered when performing genotype‐phenotype correlations in the families to confirm the causality of these variants. In conclusion, by screening known CHD‐associated genes in well‐selected nonsyndromic CHD families and cautious variant interpretation, potential causative variants were identified in less than half of the families (6 out of 13; 46%). Variant interpretation remains a major challenge reflecting the complex genetic cause of CHD. 2015 Wiley Periodicals, Inc.