Low prevalence and variable clinical presentation of troponin I and troponin T gene mutations in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disorder caused by mutations in cardiac sarcomeric proteins. Troponin I (TNNI3) and troponin T (TNNT2) are important parts of the sarcomere in heart muscle, and mutations in their genes are responsible for development of HCM. The prevalence of mutations in these two genes is low; hence, the data on clinical outcome are scarce. Yet, some of these mutations were shown to be malignant with a high incidence of sudden death. Here, we describe the disease course in three families affected with TNNI3 and one family with TNNT2 gene mutations. In TNNI3-HCM, the phenotypic manifestation ranged from clinically silent to sudden cardiac death with the worst prognosis observed in carriers of Ala157Val mutation in exon 7. In contrast, TNNT2-HCM was associated with favorable prognosis. Thus, the findings of the present study add evidence on the phenotypic presentation of this genetic disease.