Publication

Abstract : Although sporadic cases of familial restrictive cardiomyopathy (RCM) have been reported, there is limited data on whether a distinct genetic entity exists.Methods: We recognized a large family in which 5 individuals died suddenly and several surviving relatives had symptoms of heart disease. Our index case was a 49-year-old male who had onset of heart failure symptoms since the age of 40 years. Echocardiography revealed bi-atrial enlargement accompanied by a restrictive filling pattern, and normal systolic function. He had recurrent admissions for heart failure and died within 1 month of initial admission. We applied a candidate gene approach to our index case and family members that were willing for genetic analysis.Results: We identified a novel heterozygous missense mutation in exon 7 of the TNNI3 gene that results in the amino acid substitution of Tryptophan for Arginine at codon 145. The TNNI3 gene encodes a highly conserved region of the cardiac troponin I (cTnI) gene. Five other members of the family were detected to be carriers of the same mutation, among which two members had a similar restrictive filling pattern and biatrial dilation on echocardiography.