BACKGROUND: Left ventricular noncompaction of the myocardium (LVNC) has been 
recognized as a cardiomyopathy with a genetic etiology. Mutations in genes 
encoding sarcomere proteins were shown to be associated with LVNC. We evaluated 
the potential clinical impact of genetic analysis of sarcomere genes in patients 
with LVNC.
METHODS AND RESULTS: We identified 5 mutations in cardiac myosin-binding protein 
C (MYBPC3) and 2 mutations in α-tropomyosin (TPM1) in a cohort of unrelated 
adult probands with isolated LVNC. The mutations in MYBPC3 and TPM1 and in 6 
other previously reported sarcomere genes in this cohort resulted in a total of 
18 (29%) heterozygous mutations in 63 probands. β-myosin heavy chain (MYH7) was 
the most prevalent disease gene and accounts for 13% of cases, followed by 
MYBPC3 (8%). Comparing sarcomere mutation-positive and mutation-negative LVNC 
probands showed no significant differences in terms of average age, myocardial 
function, and presence of heart failure or tachyarrhythmias at initial 
presentation or at follow-up. Familial disease was found in 16 probands of whom 
8 were sarcomere mutation positive. Nonpenetrance was detected in 2 of 8 
mutation-positive families with LVNC.
CONCLUSIONS: Mutations in sarcomere genes account for a significant (29%) 
proportion of cases of isolated LVNC in this cohort. The distribution of disease 
genes confirms genetic heterogeneity and opens new perspectives in genetic 
testing in patients with LVNC and their relatives at high risk of inheriting the 
cardiomyopathy. The presence or absence of a sarcomere gene mutation in LVNC 
cannot be related to the clinical phenotype.