TitleNovel Mutations in Indian Population with Cardiomyopathies.
Publication TypeJournal Article
Year of Publication2023
AuthorsRani DSelvi, Kasala A, Dhandapany PS, Muthusami U, Kunnoth S, Rathinavel A, Ayapati DRakshak, Thangaraj K
JournalPharmgenomics Pers Med
Date Published2023

BACKGROUND: Mutations in Myosin Binding Protein C () are one of the most frequent causes of cardiomyopathies in the world, but not much data are available in India.

METHODS: We carried out targeted direct sequencing of in 115 hypertrophic (HCM) and 127 dilated (DCM) cardiomyopathies against 197 ethnically matched healthy controls from India.

RESULTS: We detected 34 single nucleotide variations in , of which 19 were novel. We found a splice site mutation [(IVS6+2T) T>G] and 16 missense mutations in Indian cardiomyopathies [5 in HCM; E258K, T262S, H287L, R408M, V483A: 4 in DCM; T146N, V321L, A392T, E393K and 7 in both HCM and DCM; L104M, V158M, S236G, R272C, T290A, G522E, A626V], but those were absent in 197 normal healthy controls. Interestingly, we found 7 out of 16 missense mutations (V158M, E258K, R272C, A392T, V483A, G522E, and A626V) in were altering the evolutionarily conserved native amino acids, accounted for 8.7% and 6.3% in HCM and DCM, respectively. The bioinformatic tools predicted that those 7 missense mutations were pathogenic. Moreover, the co-segregation of those 7 mutations in families further confirmed their pathogenicity. Remarkably, we also identified compound mutations within the gene of 6 cardiomyopathy patients (5%) with more severe disease phenotype; of which, 3 were HCM (2.6%) [(1. K244K + E258K + (IVS6+2T) T>G); (2. L104M + G522E + A626V); (3. P186P + G522E + A626V]; and 3 were DCM (2.4%) [(1. 5'UTR + A392T; 2. V158M+G522E; and 3.V158M + T262T + A626V].

CONCLUSION: The present comprehensive study on has revealed both single and compound mutations in and their association with disease in Indian Population with Cardiomyopathies. Our findings may perhaps help in initiating diagnostic strategies and eventually recognizing the targets for therapeutic interventions.

Alternate JournalPharmgenomics Pers Med
PubMed ID37750083
PubMed Central IDPMC10518145