Two founder mutations in the alpha-tropomyosin and the cardiac myosin-binding protein C genes are common causes of hypertrophic cardiomyopathy in the Finnish population

Abstract

Background. Hypertrophic cardiomyopathy (HCM) is predominantly caused by a large number of various mutations in the genes encoding sarcomeric proteins. However, two prevalent founder mutations for HCM in the alpha-tropomyosin (TPM1-D175N) and myosin-binding protein C (MYBPC3-Q1061X) genes have previously been identified in eastern Finland. Objective. To assess the prevalence of these founder mutations in a large population of patients with HCM from all over Finland. Patients and methods. We screened for two founder mutations (TPM1-D175N and MYBPC3-Q1061X) in 306 unrelated Finnish patients with HCM from the regions covering a population of ∼4,000,000. Results. The TPM1-D175N mutation was found in 20 patients (6.5%) and the MYBPC3-Q1061X in 35 patients (11.4%). Altogether, the two mutations accounted for 17.9% of the HCM cases. In addition, 61 and 59 relatives of the probands were found to be carriers of TPM1-D175N and MYBPC3-Q1061X, respectively. The mutations showed regional clustering. TPM1-D175N was prevalent in central and western Finland, and MYBPC3-Q1061X in central and eastern Finland. Conclusion. The TPM1-D175N and MYBPC3-Q1061X mutations account for a substantial part of all HCM cases in the Finnish population, indicating that routine genetic screening of these mutations is warranted in Finnish patients with HCM.

Key words::

• Alpha-tropomyosin
• Finnish population
• founder mutation
• hypertrophic cardiomyopathy
• myosin-binding protein C

Acknowledgements

We thank Raija Miettinen, MSc, Teemu Kuulasmaa, MSc, Satu Nenonen, RN, Eila Ruotsalainen, RN, and Sini Weckström, RN, for assistance in data collection.

This study has previously been presented as an abstract in Florence International Course on Advances in Cardiomyopathies, 2008 (J.K.)

Declaration of interest: The authors state no conflict of interest. This study was supported by the Academy of Finland, the Finnish Foundation for Cardiovascular Research and the Kuopio University Hospital (grants to J.K.). T.H. has received grants from the Finnish foundation for Cardiovascular Research, Finnish Medical Foundation, the special governmental subsidy for health sciences research, and the Helsinki University Central Hospital.