A Complete Absence of Missense Mutation in Myosin Regulatory and Essential Light Chain Genes of South Indian Hypertrophic and Dilated Cardiomyopathies.

ABSTRACT

BACKGROUND: Myosin is a hexameric contractile protein composed of 2 heavy chains associated with 4 light chains of 2 distinct classes - 2 regulatory light chains (MYL2) and 2 essential light chains (MYL3). The myosin light chains stabilize the long alpha helical neck of the myosin head and regulate the myosin ATPase activities. OBJECTIVES: Mutations in MYL2 and MYL3 are reported to be associated with cardiomyopathies. However, there is no study available on these genes in Indian cardiomyopathies, and therefore we planned to study them. METHOD: For the first time we sequenced MYL2 and MYL3 genes in a total of 248 clinically well-characterized cardiomyopathies consisting of 101 hypertrophic and 147 dilated cases along with 207 healthy controls from south India. RESULTS: Our study revealed a total of 10 variations - 7 in MYL2 and 3 in MYL3, of which 3 are novel variations observed exclusively in cases. However, the 15 causative missense mutations previously reported are totally absent in our study, which showed that the sequences of MYL2 and MYL3 are highly conserved in Indian cases/controls. CONCLUSIONS: MYL2 and MYL3 mutations are rare and the least cause of cardiomyopathies in Indians.