Key result
Review identifies 45 sarcomeric variants linked to sudden cardiac death in Indian HCM patients.
Why the study?
The study aimed to determine the scope of available literature on sarcomere protein variants associated with sudden cardiac death reported among Indian patients with hypertrophic cardiomyopathy.
What are the sarcomeric gene variants associated with sudden cardiac death among Indian patients with hypertrophic cardiomyopathy?
Systematic Review
What are the sarcomeric gene variants associated with sudden cardiac death among Indian patients with hypertrophic cardiomyopathy?
This scoping review compiles pathogenic sarcomeric gene variants associated with sudden cardiac death in Indian HCM patients into a freely accessible database (HCMvar).
May inform ancestry-specific genetic screening in Indian HCM; extends global variant catalogs with South Asian data.
Hypertrophic cardiomyopathy (HCM) is a genetic heart muscle disease that frequently causes sudden cardiac death (SCD) among young adults. Several pathogenic mutations in genes encoding the cardiac sarcomere have been identified as diagnostic factors for HCM and proposed as prognostic markers for SCD. The objective of this review was to determine the scope of available literature on the variants encoding sarcomere proteins associated with SCD reported among Indian patients with HCM. The eligibility criteria for the scoping review included full text articles that reported the results of genetic screening for sarcomeric gene mutations in HCM patients of Indian south Asian ancestry. We systematically reviewed studies from the databases of Medline, Scopus, Web of Science core collection and Google Scholar. The electronic search strategy included a combination of generic terms related to genetics, disease and population. The protocol of the study was registered with Open Science Framework (https://osf.io/53gde/). A total of 19 articles were identified that reported pathogenic or likely pathogenic (P/LP) variants within MYH7, MYBPC3, TNNT2, TNNI3 and TPM1 genes, that included 16 singletons, one de novo and one digenic mutation (MYH7/ TPM1) associated with SCD among Indian patients. Evidence from functional studies and familial segregation implied a plausible mechanistic role of these P/LP variants in HCM pathology. This scoping review has compiled all the P/LP variants reported to-date among Indian patients and summarized their association with SCD. Single homozygous, de novo and digenic mutations were observed to be associated with severe phenotypes compared to single heterozygous mutations. The abstracted genetic information was updated with reference sequence ID (rsIDs) and compiled into freely accessible HCMvar database, available at https://hcmvar.heartfailure.org.in/. This can be used as a population specific genetic database for reference by clinicians and researchers involved in the identification of diagnostic and prognostic markers for HCM.
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Koshy et al. (2023) conducted a systematic review in Hypertrophic cardiomyopathy (HCM). Pathogenic or likely pathogenic (P/LP) variants in sarcomeric genes was evaluated on Catalog of P/LP variants in sarcomeric genes associated with sudden cardiac death. A scoping review identified 45 distinct pathogenic or likely pathogenic sarcomeric gene variants across 19 studies associated with sudden cardiac death in Indian patients with hypertrophic cardiomyopathy.
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