[Novel GATA4 mutations identified in patients with congenital atrial septal defects].
OBJECTIVE
To identify the genetic defects in patients with congenital atrial septal defects (ASD).


METHODS
The clinical data and blood samples from 180 unrelated subjects with congenital ASD were collected and evaluated. Two hundred healthy individuals served as controls. The coding exons and the flanking introns of GATA4 gene were amplified by polymerase chain reaction and sequenced using the di-deoxynucleotide chain termination approach. The acquired sequences were aligned with the sequences publicized in GenBank by the aid of programme BLAST to identify the sequence variations. Clustal W software was applied for analysis of the conservation of altered amino acids.


RESULTS
Two novel heterozygous missense GATA4 mutations were identified in 2 out of 180 ASD patients. Namely, the triplet substitutions of GTC for GGC at codon 21 and TCG for CCG at codon 87 were detected, predicting the conversions of glycine into valine at amino acid residue 21 (G21V) and proline into serine at amino acid residue 87 (P87S). None of the two mutations were detected in 200 healthy controls. Across-species alignment of GATA4 encoded protein sequences displayed that the mutated amino acids were highly conserved evolutionarily. Additionally, a single nucleotide polymorphism c.99G>T was observed. However, the polymorphic frequency distribution in ASD cases was similar with that in healthy controls (for genotype GT, χ(2) = 0.7556, P = 0.3847; for allele T, χ(2) = 0.7235, P = 0.3950).


CONCLUSIONS
Two novel mutations of GATA4 gene are identified in two unrelated ASD patients. This finding provides new insight into the molecular etiology responsible for ASD.
Department of Paediatrics, Tongji Hospital of Tongji University, Shanghai 200065, China.
Xing-Yuan
XY
Liu
Yi-Qing
YQ
Yang
Jun
J
Ma
Xiao-Ping
XP
Lin
Jing-Hao
JH
Zheng
Kai
K
Bai
Yi-Han
YH
Chen
D016022:Case-Control Studies; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D050991:GATA4 Transcription Factor / Q000235:genetics*; D016678:Genome; D006344:Heart Septal Defects, Atrial / Q000235:genetics*; D006801:Humans; D009154:Mutation
D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human