A novel in-frame deletion in the KCNQ۱ gene and an AKAP۹ variant in Iranian patients with long-QT syndrome

Background and Aim: Congenital Long-QT syndrome represents a heterogeneous disorder leading primarily to sudden cardiac death (SCD) in the young. Two symptomatic patients with a family history of eight SCDs in an Iranian pedigree prompted us to identify and characterize the underlying genetic basis.Methods: Whole exome sequencing and DNA Sanger sequencing were performed for genotype determination of the patients. Different predictive tools followed by family study were employed for the pathogenicity prediction of the variants.Results: A reported heterozygous variant (rs۱۳۹۹۶۵۳۷۳) in AKAP۹ gene was identified by whole exome sequencing but a novel in-frame deletion in the KCNQ۱ gene (c.۴۰_۵۵delCGCTGGGGTTGGGGC) was revealed through DNA Sanger sequencing. The latter was detected in all patients but none of the healthy family members.Conclusion: Identification of the novel mutation in Iranian patients not only supports the genetic modifier effect of the AKAP۹ variant but also indicates the next generation sequencing disadvantage as an opening and exclusive method for the genetic diagnosis of Long-QT syndrome.