Identification and functional analysis of a novel HANDI mutation associated with congenital ventricular septal defect

Objective: To identify the novel HAND1 mutation associated with congenital ventricular septal defect (VSD) and to perform the functional analysis. Methods: A total of 125 patients with congenital VSD and 210 control individuals were recruited, and their clinical data and blood samples were collected. The genomic DNA from each study subject was isolated, and all the coding exons of HAND 1 were amplified. The amplicons from HAND 1 were sequenced to identify a sequence variation. The functional characteristics of the mutant HAND 1 were analyzed by a dual-luciferase reporter assay system. Results: A novel heterozygous HAND1 mutation c.355G>T, equivalent to E119X, was identified in a patient with sporadic VSD. This nonsense mutation was absent in the 210 control subjects. Functional analysis revealed that the mutant HAND 1 lost the ability to transactivate a target gene. Conclusion: A novel HAND1 mutation with VSD is identified in this study.