Gene Mutations in Apical Hypertrophic Cardiomyopathy

• DOI: 10.1161/circulationaha.105.547448
• Publication Date: 2005-11-02T21:38:28Z
• Authors: Michael Arad; Manual Penas-Lado; Lorenzo Monserrat; Barry J. Maron; Mark Sherrid; Carolyn Y. Ho; Scott Barr; Ahmad Karim; Timothy M. Olson; Mitsohiro Kamisago; J.G. Seidman; Christine E. Seidman
• Keywords: Proband

Background— Nonobstructive hypertrophy localized to the cardiac apex is an uncommon morphological variant of hypertrophic cardiomyopathy (HCM) that often further distinguished by distinct giant negative T waves and a benign clinical course. The genetic relationship between HCM with typical morphology versus isolated apical incompletely understood. Methods Results— Genetic cause was investigated in 15 probands DNA sequence analyses 9 sarcomere protein genes 3 other ( GLA , PRKAG2 LAMP2 ) implicated idiopathic hypertrophy. Six gene mutations were found 7 samples; no samples contained or . Clinical evaluations demonstrated familial 4 probands, disease-causing identified. Two families shared actin Glu101Lys missense mutation; all members both manifestations (n=16) had An essential light chain mutation Met149Val caused midventricular segment another proband 5 family members, but 6 affected relatives morphologies. No identified remaining members. Conclusions— Sarcomere rather than more common morphologies reflect interactions among etiology, background modifier genes, and/or hemodynamic factors. Only limited number defects (eg, Glu101Lys) consistently produce HCM.