Introduction: Sudden cardiac deaths caused by cardiac arrhythmias (long QT’s) have a prevalence of about 1:2000-2500 in different populations worldwide. Individuals affected with life threatening arrhythmias typically exhibit episodes of syncope, palpitations, seizures, abnormal ECG pattern. These are autosomal dominant disorders. Mutations identified in three genes (KCNQ1, KCNH2 and SCN5A) account for majority of the cases.
Methods: The aim of the ongoing study is to identify the mutations and SNPs in long QT type 1, 2 and 3 patients by sequencing all the coding exons in three genes. Till now, we have included eighteen patients in our study, Here, we report here two cases clinically diagnosed and molecularly confirmed with Long QT (Type 1 and 3) syndrome.
Results: A 12 year old girl with history of hundred episodes of syncope and QT prolongation was referred for evaluation. Mutational analysis identified a known heterozygous missense mutation (V411M) in the SCN5A gene, encoding the primary cardiac voltage gated sodium channel, Nav 1.5. Second case is 2 year old boy with QTc of 510 ms. Sequencing identified a known heterozygous in frame 3 bp deletion (S277del), that causes a decrease in the K+ channel activity. Screening of his parents detected this mutation in the asymptomatic father.
A polymorphism (H558R) was also identified in four out of nine patients screened for mutation analysis in SCN5A gene. Functional studies have shown the association of this polymorphism with the prolongation of QT interval.
Conclusions: This study allows confirmation of the clinical diagnosis and provides information regarding choice of adopting the appropriate therapeutic and preventive intervention.