Heterogeneity of Clinical Manifestation of Hypertrophic Cardiomyopathy Caused by Deletion of Lysine 183 in Cardiac Troponin I Gene

Insight From Two Autopsy Cases With an Identical Sarcomeric Gene Mutation

Abstract

Hypertrophic cardiomyopathy (HCM) is associated with gene mutations that encode sarcomeric proteins. However, the relationship between genotype and histopathologic findings is unclear. We report on two autopsy cases with advanced HCM associated with deletion of lysine 183 mutation in the cardiac troponin I gene. One case, a 74-year-old female exhibited dilated cardiomyopathy-like features. Transmural scarring was diffuse and circumferential, involving the whole left ventricle, especially the ventricular septum which was replaced with extensive fibrosis and showed marked wall thinning. The other case, a 92-year-old male revealed typical HCM findings. Patchy scars which corresponded to replacement fibrosis were found extending from the septum to the anterior wall. These two autopsy cases indicate the clinical heterogeneity of HCM even within the same disease-causing mutation and suggest that the degree and extent of fibrosis determine differences in the clinical manifestations of HCM. This is the first autopsy report that demonstrates identical sarcomeric gene mutations causing different clinical manifestations and histologic findings. The findings suggest that additional genetic or environmental factors influence the phenotypic expressions and clinical courses of HCM caused by genetic mutation of sarcomeric proteins.