A rare mutation in lamin A gene is associated with dilated cardiomyopathy in Indian patients

Abstract

Mutations in lamin A gene (LMNA) are associated with a number of genetic diseases that are collectively termed laminopathies. Most LMNA mutations cause muscular dystrophies and cardiomyopathies. The incidence of LMNA mutations in familial dilated cardiomyopathy (DCM) patients is 5-8 % in Caucasian populations. However, there is no large scale study of LMNA mutations in Indian DCM patients. Hence, we have carried out sequence analysis of LMNA in 239 Indian DCM patients. We have identified a rare non-synonymous mutation c.1873A>T in one patient, which predicted a change in the amino acid serine to cysteine at residue 625. In addition we also identified 20 synonymous single nucleotide polymorphisms in 28 patients. The c.1873A>T mutation was absent in 156 healthy and ethnically matched controls. The serine at position 625 has been earlier identified as a mitotic phosphorylation site in lamin A. Expression of mutant lamin S625C in cultured cells led to a decrease in levels of cyclin dependent kinase inhibitor p21, suggesting compromised cell cycle regulation in these cells. Our study provides important information on the extent of variations in LMNA in Indian DCM patients and identifies a rare mutation in LMNA that is likely to cause deleterious effects on cellular functions.