A novel mutation of GATA4 (K319E) is responsible for familial atrial septal defect and pulmonary valve stenosis.

Congenital heart disease (CHD) is the most common birth defect in humans, and the etiology of most CHD remains to be elusive. Atrial septal defect (ASD) makes up 30–40% of all adult CHDs and is thought to be genetically heterogeneous. Previous studies have demonstrated that mutations in transcription factors e.g. NKX2.5, GATA4, and TBX5 contribute to congenital ASD. In this study, we investigate a family of three generations with seven patients with ASD and pulmonary valve stenosis (PS). A novel GATA4 mutation, c.955ANG (p.K319E), was identified and co-segregated with the affected patients in this family. This mutation was predicted to be deleterious by three different bioinformatics programs (The polyphen2, SIFT and MutationTaster). Our finding expands the spectrum of GATA4 mutations and provides additional support that GATA4 plays important roles in cardiac development.