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