title: A novel GATA6 mutation associated with congenital ventricular septal             defect.
abstract: Ventricular septal defect (VSD) is the most common form of congenital cardiovascular             malformation and an important contributor to the substantially increased morbidity             and mortality in infants. Emerging evidence indicates the genetic basis for the             pathogenesis of congenital VSD in a significant proportion of patients. However,             congenital VSD is a genetically heterogeneous disease and the genetic defects             responsible for VSD in the overwhelming majority of cases remain unclear. In this             study, the entire coding region of the GATA6 gene, which encodes a zinc-finger             transcription factor crucial to normal cardiogenesis, was sequenced in 130 unrelated             patients with congenital VSD. The available relatives of the index patient carrying             the identified mutation and 200 unrelated ethnically matched healthy individuals             used as controls were subsequently genotyped. The functional characteristics of             the mutant GATA6 were assessed in contrast to its wild-type counterpart using             a luciferase reporter assay system. As a result, a novel heterozygous missense             GATA6 mutation, p.G220S, was identified in a proband with VSD. The variation was             absent in 400 control chromosomes and the altered amino acid was highly conserved             evolutionarily across species. Genetic analysis of the family members of the mutation             carrier showed that the substitution co-segregated with VSD was inherited as an             autosomal dominant trait. Functional analysis demonstrated that the p.G220S mutation             of GATA6 was associated with significantly decreased transcriptional activity.             The findings provide novel insight into the molecular mechanism involved in VSD,             implying the potential clinical implications in the gene-specific prophylaxis             and therapy of this common developmental abnormality in neonates.
authors.affiliation: Department of Pediatrics, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, PR China.
authors.forename: Gui-Fen
authors.initials: GF
authors.lastname: Zheng
authors.forename: Dong
authors.initials: D
authors.lastname: Wei
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.forename: Ning
authors.initials: N
authors.lastname: Zhou
authors.forename: Yi-Qing
authors.initials: YQ
authors.lastname: Yang
authors.forename: Xing-Yuan
authors.initials: XY
authors.lastname: Liu
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D050993:GATA6 Transcription Factor / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D057809:HEK293 Cells; D006345:Heart Septal Defects, Ventricular / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D010641:Phenotype; D016415:Sequence Alignment; D013045:Species Specificity; D014158:Transcription, Genetic
chemical_list: D050993:GATA6 Transcription Factor; C494759:GATA6 protein, human