Detection and clinical value of novel GATA6 mutations associated with congenital atrial septal defects

Abstract

Objective To identify novel mutations in the GATA6 gene associated with congenital atrial septal defects (ASD). Methods This was a case-control study.A cohort of 220 unrelated Han-race patients with congenital ASD and 200 unrelated ethnically matched healthy individuals used as controls, who were admitted to Tongji University Affiliated Tongji Hospital from January, 2007 to October, 2011, were recruited.The peripheral venous blood samples from the participants were prepared.All the coding exons and their flanking sequences of the GATA6 gene were amplified by polymerase chain reaction and sequenced using the di-deoxynucleotide chain termination technique.The acquired sequences were aligned with the sequences derived from GenBank by BLAST to identify the sequence variations.The software ClustalW was used to analyze the conservation of the altered amino acids. Results Three novel heterozygous missense GATA6 mutations, c.250G>A (p.A84T), c.649G>C (p.G217R) and c.1270A>C (p.S424R), were identified in 3 of 220 ASD patients, respectively.None of the three mutations was detected in 200 healthy control individuals.A cross-species alignment of GATA6 encoded protein sequences showed that the mutated amino acids were relatively conserved evolutionarily. Conclusion The identification of novel GATA6 mutations associated with ASD contributes to the reveal of the mechanism involved in the pathogenesis of ASD.（Chin J Lab Med,2012,35:1108-1111） Key words: Heart septal defects; atrial; GATA6 transcription factor; Mutation