AUTHOR=Martin Lisa J. , Pilipenko Valentina , Benson D. Woodrow TITLE=Role of Segregation for Variant Discovery in Multiplex Families Ascertained by Probands With Left Sided Cardiovascular Malformations JOURNAL=Frontiers in Genetics VOLUME=Volume 9 - 2018 YEAR=2019 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2018.00729 DOI=10.3389/fgene.2018.00729 ISSN=1664-8021 ABSTRACT=
Cardiovascular malformations (CVM) are common birth defects (incidence of 2–5/100 live births). Although a genetic basis is established, in most cases the cause remains unknown. Analysis of whole exome sequencing (WES) in left sided CVM case and trio series has identified large numbers of potential variants but evidence of causality has remained elusive except in a small percentage of cases. We sought to determine whether variant segregation in families would aid in novel gene discovery. The objective was to compare conventional and co-segregation approaches for WES in multiplex families. WES was performed on 52 individuals from 4 multiplex families ascertained by probands with hypoplastic left heart syndrome (HLHS). We identified