Detection of Variants in Patients with Idiopathic Ventricular Fibrillation by Whole-exome Sequencing

Idiopathic ventricular fibrillation (IVF) is a cause of sudden cardiac death (SCD). The frequency of mutations in disease-causing genes ranges, on average, between 16 and 48% in SCD cases. This study aimed to identify novel mutations in IVF patients without KCNQ1, KCNH2, and SCN5A mutations using whole-exome sequencing (WES).

Genomic DNA extracted from peripheral blood samples obtained from five patients with IVF and WES was used to identify mutations associated with IVF. Candidate variants were validated by Sanger sequencing.

Four patients harbored suspected mutations in 100 inherited cardiomyopathy-and channelopathy-associated genes (e.g., TCAP, TTN, MYPN, CACNA1C, and TNNT2). All of these genetic variants have been given a dbSNP rs number; however, their clinical significance remains unknown. Bioinformatics tools predicted severe functional disruptions in the loci harboring these suspected mutations, suggesting their pivotal roles in IVF.

This study revealed the effectiveness of WES for IVF patients without KCNQ1, KCNH2, and SCN5A mutations. Although it is difficult to interpret broad WES results, the analysis can provide insight into the etiology of a heterogeneous disease.