A novel mutation in GJA۱ gene in an Iranian Family with non-syndromic congenital heart disease; Detection by whole exome sequencing

Background and Aim: Congenital heart diseases (CHDs) is the most common congenital malformation which occur in newborns. Studies demonstrate that genetic and environmental factors involve in the CHD etiology. The new genomic technology, i.e., the next generation sequencing, has been an informative and fast approach in identification of disorders genetic causes. So, we investigated the genetic cause of CHD in an Iranian family with two affected individuals, i.e., son and mother of the family suffer from CHD.Methods: Whole-exome sequencing (WES) was carried out on DNA sample of the family’s probond who was a ۱۰ years old boy with atrioventricular septal defect (AVSD). PCR and Sanger sequencing was performed for confirmation and segregation analysis of the identified variants.Results: A novel, heterozygous indel GJA۱ variant, c.۹۳۲delC (p.Ala۳۱۱fs) was found in the proband and mother of the family. This variant has not been reported in different public variant databases and bioinformatics analysis indicates to be the likely cause of non-syndromic CHD in this family.Conclusion: In the present study, for the first time we report a novel heterozygous indel variant on the GJA۱ gene in an Iranian family with non-syndromic CHD which expands our understanding of the CHD causative agents.

Keywords:

Congenital heart disease , Whole-exome sequencing , Gap Junction Protein Alpha ۱ (GJA۱)