Abstract 2978: Genotype-Phenotype Variations in Cardiomyopathies Caused by a Cardiac Troponin I Gene Mutation
Introduction: It has been reported that mutations in the cardiac troponin I (TNNI3) gene are associated with variable phenotypes of cardiomyopathies. However, there is no report that demonstrated 3 different phenotypes (hypertrophic cardiomyopathy; HCM, restrictive cardio-myopathy and dilated cardiomyopathy) caused by an identical mutation in the TNNI3 gene.
Hypothesis: We assessed the hypothesis that carriers of familial HCM with a single TNNI3 gene mutation may show not only phenotypes of HCM, but also phenotypes of restrictive cardiomyopathy and dilated cardiomyopathy.
Methods: Four hundred probands with HCM were screened for mutations in the TNNI3 gene with the polymerase chain reaction and single strand conformational polymorphism analysis.
Results: We detected a Lys183del mutation in 13 (3.3%) of 400 probands with HCM. Family studies were performed, and 54 carriers with the Lys183del mutation were identified. Besides the typical features of HCM (Figure A⇓), such as non-dilated left ventricle and preserved systolic function (n = 30, 55% of 54 carriers), phenotypes of restrictive cardiomyopathy (Figure B⇓) were found in 1 (1.9%) carrier, and phenotypes of dilated cardiomyopathy (Figure C, D⇓) in 5 (9.3%) carriers. Of the 54 carriers, 18 (33%) did not manifest left ventricular hypertrophy on echocardiography.
Conclusions: In conclusion, 3 different phenotypes of cardiomyopathies were found to be caused by an identical TNNI3 gene mutation, suggesting a hereditary overlapping in cardiomyopathies.