A novel mutation of GATA4 in a familial atrial septal defect

Abstract Background Previous studies have identified that mutations in a few genes, including T-BOX5 , NKX2-5 , EVC and GATA4 , are associated with atrial septal defect (ASD). Methods A family of three generations with 4 members who were affected with ASD was investigated. To exclude the presence of any sub-microscopic chromosomal imbalance, high-resolution 1M array-based comparative genomic hybridization (aCGH) was performed. SNaPShot was used to certify the specificity of the finding mutation in the other family members. The coding region of GATA4 and NKX2-5 genes was screened by sequencing in another 30 cases including 10 cases of ventricular septal defect (VSD), 10 cases of atrial septal defect (ASD), 8 cases of VSD combined with ASD and 2 cases of atrioventricular septal defects (AVSD). Results No pathogenic copy number variant was detected by aCGH in the four affected family members with ASD. A novel non-synonymous variant, c.839C>T (T280M) in GATA4 , was identified and segregated with all the ASD patients within this Chinese family. Such mutation was absent in other family members or present among sporadic CHD patients. In addition, we identified a non-synonymous variant in the NKX2-5 gene (P257A) associated with one congenital heart disease patient with VSD. Both mutations were not identified among healthy controls. Conclusion T280M mutation of GATA4 is suggested to be associated with ASD in this Chinese family.