Genotyping of Cardiac channelopathies: Indian data

posted Jan 25, 2017, 11:30 PM by sourav ghosh   [ updated Jan 26, 2017, 3:01 AM ]
Bijal Vyas
University School of Medical & Paramedical Sciences, Guru Gobind Singh Indraprastha University, New Delhi, India

Introduction: Cardiac channelopathies have a prevalence of about 1:2000-2500 in different populations worldwide. The common life threatening cardiac channelopathies, Long QT (LQTS type 1-13) and Brugada (BrS type 1-12) present with syncope/ palpitations/ seizures/ aborted cardiac arrest. They have incomplete penetrance and variable expressivity. The three common genes (KCNQ1, KCNH2 and SCN5A) account for 75% of all LQTS cases, and SCN5A in BrSaccounts for 25% of all cases.
Aim: To identify the causative variation in the associated genes responsible for causing cardiac channelopathies in Indian patients.
Materials & Methods: Fifty patients who fulfilled the inclusion criteria of the study were enrolled. Mutation analysis was performed in most probable candidate gene by direct sequencing. If a mutation was not identified, NGS was performed to identify mutations in other cardiac genes. Parents and siblings were screened if a mutation was identified in the proband. Novel mutations were evaluated for pathogenicity using bioinformatics and molecular modeling softwares.
Results: Mutations was identified in twenty-five patients by Sanger sequencing, twenty-two had LQTS and three were affected with BrS. Among the LQT syndromes, mutations were identified in nineteen in KCNQ1 (LQTS1), one in KCNH2 (LQTS2)and two in SCN5A (LQTS3). Among the LQTS1 patients, ten were identified with biallelic mutations. The three BrS patients had mutations in SCN5A, agene responsible for BrS1. Eleven of twenty-five mutations were novel. NGS identified mutation in twelve of the remaining twenty-five patients. Of which, ten had LQTS and two had BrS. Of these mutations, seven were novel. 
Conclusion: Genotyping is important for confirming type of LQTS/ BrS, which has implications for management, and identification of asymptomatic at risk individuals.

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