Novel GATA4 mutations in patients with congenital ventricular septal defects

Abstract

Objective To identify novel GATA4 mutation in patients with congenital ventricular septal defects(VSD).Methods The clinical data and blood samples from 160 unrelated subjects with congenital VSD were collected and evaluated in contrast to 200 healthy individuals.The sequenced of coding exons and the flanking introns of GATA4 gene were amplified by PCR and sequenced using the dideoxynucleotide chain termination approach.The acquired sequences were aligned with the sequences publicized in GenBank by the aid of programme BLAST to identify the sequenece variations.The software Clustal W was applied to analysis of the conservation of altered amino acids.Results Three novel heterozygous missense GATA4 mumtations were identified in 3 of 160 VSD patients,respectively.Namely,the triplet substitutions of GGC for AGC at codon 191,ATG for GTG at codon 267,and ATG for GTG at codon380,predicting the conversions of serine into glycine at amino acid residue 191(S191G),valine into methionine at amino acid residue 267(V267M),and valine into methiomne at amino acid residue 380(V380M)were detected.None of the three mutations were observed in 200 healthy controls.A cross-species alignment of GATA4 encoded protein sequences displayed that the valine at amino acid residue 267 was highly conserved evolutionarily.Additionally,a single nucleotide polymorphism c.99G > T was observed.However,the polymorphic frequency distribution in VSD cases(GG geuotype 87.5%,GT genotype 12.5%,TT genotype 0%)were not statistically different from that in healthy controls(GG genotype 93.0%,GT genotype 7.0%,TT genotype 0%,for genotype,χ~2 = 3.144 1,P = 0.076 2 ; for alleles,χ~2 = 2.987 7,P=0.083 9).Conclusions Novel GATA4 mutations are identified in patients with congenital VSD,providing new insight into the molecular etiology responsible for VSD.These findings would be helpful the early prophylaxis and specific therapy for VSD. Key words: Heart septal defects,ventricular; GATA4 transcription factor; Mutation