Abstract 3450: Mutations in Cardiac Myosin-Binding Protein C (MYBPC3) and α-Tropomyosin (TPM1) in Left Ventricular Noncompaction
Left ventricular noncompaction (LVNC) constitutes a primary cardiomyopathy characterized by a severely thickened, two-layered myocardium, numerous prominent trabeculations, and deep intertrabecular recesses. Recently, mutations in genes encoding sarcomere proteins β-myosin heavy chain (MYH7), α-cardiac actin (ACTC), and cardiac troponin T (TNNT2) were shown to be associated with LVNC. We investigated weather mutations in cardiac myosin-binding protein C (MYBPC3) and α-tropomyosin (TPM1) may also lead to LVNC. Mutational analysis of MYBPC3 and TPM1 was carried out in a cohort of 63 Caucasian adult probands (mean age, 40 years) with isolated LVNC. Denaturing high performance liquid chromatography (DHPLC) analysis and direct DNA sequencing were performed. The diagnosis of LVNC was made by echocardiography based on established criteria: a severely thickened, two-layered ventricular myocardium with a noncompacted / compacted ratio of ≥ 2, prominent and excessive trabeculations, and deep intertrabecular recesses filled with blood from the ventricular cavity as visualized by colour Doppler imaging. Heterozygous mutations were identified in 7 of 63 samples, 5 in MYBPC3, and 2 in TPM1. LVNC was diagnosed at an age range from 20 to 70 years. Symptoms at initial diagnosis were diverse: dyspnea, syncope, atypical chest pain, and severe congestive heart failure. The left ventricular apex was affected in 5 of 7 probands and in 2 of 5 probands only the midventricular inferior and lateral wall was involved. Left ventricular enddiastolic dimensions were enlarged and systolic function was impaired in 2 of 7 probands. In addition, an overview of the mutational analysis of 8 sarcomere protein genes in this cohort of patients with LVNC will be given. MYH7 was the most prevalent disease gene and accounts for 13% of cases followed by MYBPC3 as the second most frequent disease gene (8%). Our findings confirm that LVNC belongs to the spectrum of cardiomyopathies originating in molecular defects of the sarcomere.