A new common mutation in the cardiac beta-myosin heavy chain gene in Finnish patients with hypertrophic cardiomyopathy

Abstract

Background. In the nationwide FinHCM Study including 306 Finnish patients with hypertrophic cardiomyopathy (HCM), we have previously identified two founder mutations in the alpha-tropomyosin (TPM1-D175N) and myosin-binding protein C (MYBPC3-Q1061X) genes, accounting for 18% of all cases.

Objective. To screen additional mutations, previously identified in eastern Finnish cohorts with HCM, in the FinHCM Study population.

Patients and methods. Ten mutations in the beta-myosin heavy chain gene (MYH7), TPM1, and MYBPC3 were screened.

Results. MYH7-R1053Q was found in 17 of 306 patients (5.6%). No carriers of MYH7-R719W or N696S were found. A novel TPM1-D175G mutation was found in a single patient. MYBPC3 mutations were found in 14 patients: IVS5-2A-C in two, IVS14-13G-A in two, K811del in six, and A851insT in four patients. Altogether, a HCM-causing mutation was identified in 32 patients, accounting for 10.5% of all cases. In addition, two MYBPC3 variants R326Q and V896M with uncertain pathogenicity were found in eight and in 10 patients, respectively.

Conclusion. Combining the present findings with our previous results, a causative mutation was identified in 28% of the FinHCM cohort. MYH7-R1053Q was the third most common mutation, and should be screened in all new cases of HCM in Finland.

Key words::

• Alpha-tropomyosin
• beta-myosin heavy chain
• cardiac myosin-binding protein C
• Finland
• genetics
• hypertrophic cardiomyopathy

Acknowledgements

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

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