BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a clinically heterogeneous 
genetic heart disease characterized by left ventricular hypertrophy in the 
absence of another disease that could explain the wall thickening. Elucidation 
of the genetic basis of HCM lead to the identification of several genes encoding 
sarcomeric proteins, such as MYH7, MYBPC3, TPM1, TNNT2, and TNNI3. Sarcomeric 
genes are mutated in approximately 40% of HCM patients and a possible 
explanation for the incomplete yield of mutation-positive HCM may be somatic 
mutations.
METHODS AND RESULTS: We studied 104 unrelated patients with non-familial HCM. 
Patients underwent clinical evaluation and mutation screening of 5 genes 
implicated in HCM (MYH7, MYBPC3, TPM1, TNNT2, and TNNI3) in genomic DNA isolated 
from resected cardiac tissue; 41 of 104 were found to carry a mutation, but as 
several patients carried the same mutations, the total amount of different 
mutations was 37; 20 of these mutations have been previously described, and 
pathogenicity has been assessed. To determine the effect of the 17 new mutations 
an in silico assay was performed and it predicted that 4 variants were damaging 
mutations. All identified variants were also seen in the DNA isolated from the 
corresponding blood, which demonstrated the absence of somatic mutations.
CONCLUSIONS: Somatic mutations in MYH7, MYBPC3, TPM1, TNNT2, and TNNI3 do not 
represent an important etiologic pathway in HCM.