About 1% of Indians carry mutations in genes coding for ion channels that can cause cardiac channelopathies. Credit: Vigneshwar Senthilvel
Whole-genome sequencing has uncovered genetic variants likely to cause cardiac channelopathies, a group of inherited disorders that affect the heart's electrical activity1. These mutations were not detected by whole-exome sequencing in Indian patients.
About 1% of Indians carry mutations in genes coding for ion channels that can cause the disease. Symptoms include dizziness, syncope, palpitations, and seizures in most cases. In rare cases, the symptom of onset can be cardiac arrest or sudden cardiac death. Major forms of cardiac channelopathy include long QT syndrome, Brugada syndrome, short QT syndrome, and catecholaminergic polymorphic ventricular tachycardia.
A team of researchers, led by the CSIR Institute of Genomics and Integrative Biology in Delhi, did whole-genome sequencing with DNA isolated from 25 patients at five tertiary health care centers. Whole-exome sequencing results had been negative for mutations.
Using advanced tools like ANNOVAR to furnish functional consequences of genetic variations and MANTA for structural variant identification from next generation sequencing data, the scientists analyzed changes in amino acid sequences, mutations causing protein dysfunction and structural variations.
The team identified one likely pathogenic nonsynonymous variation, one putatively causal pathogenic loss of function variation and one pathogenic structural variation. They also found 16 structural variations of unknown significance – more research is necessary to understand their role in cardiac disease.
The research underscores the need for larger genomic initiatives in India to better understand the genetic basis of these inherited disorders in South Asian populations. This could lead to improved diagnosis and treatment.
