Sarcomere protein gene mutations in patients with apical hypertrophic cardiomyopathy.

Background-Apical hypertrophic cardiomyopathy (HCM) is a unique form of HCM with left ventricular hypertrophy confined to the cardiac apex. The purpose of our study was to report genetic findings in a large series of unrelated patients with apical HCM and compare them with a nonapical HCM cohort. Methods and Results-Overall, 429 patients with HCM underwent genetic testing. The panel included 8 sarcomere protein genes and 3 other genes (GLA, PRKAG2, and LAMP2). Sixty-one patients were diagnosed with apical HCM. A positive genotype was found in 8 patients with apical HCM. The genotype-positive and genotype-negative patients had similar maximal wall thicknesses (17.5 +/- 3.5 mm versus 17.6 +/- 3.3 mm, P = 0.71) and similar frequency of HCM-related events (2/8; 25% versus 13/53; 25%; P = 0.98). Thirteen percent with apical HCM and 40% with nonapical HCM had a positive genotype (P < 0.001) most often involving the MYBPC3 and MYH7 genes. Conclusions-In apical HCM, a positive genotype was found less frequently than in nonapical HCM, and it was most often involving MYBPC3 and MYH7 genes. Only 13% of patients with apical HCM were found to be genotype positive, indicating that genome-wide association studies and gene expression profiling are needed for better understanding of the genetic background of the disease. There was no significant genotype-phenotype correlation in our cohort with apical HCM. (Circ Cardiovasc Genet. 2011;4:288-295.)