[Discovery and functional analysis of a novel ISL1 variant associated with congenital heart defect].

Objective: To analyze variation of ISL1 gene and explore its functional characteristics in relation with congenital heart defect (CHD).

Methods: Clinical data and peripheral blood samples of 194 CHD patients and 232 healthy controls were collected for the extraction of genomic DNA. The coding exons and flanking intronic regions of the ISL1 gene were sequenced. Expression plasmid for the wild-type ISL1 gene ISL1-pcDNA3.1 was constructed, and the corresponding variants were obtained by site-specific mutagenesis. The gene expression plasmid was transfected into CHO cells with liposome, and the functional characteristics of ISL1 variant were studied by double luciferase reporter gene analysis.

Results: A novel variant of the ISL1 gene c.499C>T (p.Q167X) was detected in a patient with sporadic CHD. Functional study showed that the variant has lost its transcriptional activation function for the MEF2C promoter.

Conclusion: A novel variant of the ISL1 gene related to CHD has been identified. The defect of ISL1 gene may underlay the pathogenesis for a proportion of CHD.