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.
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.
Entities:
Keywords:
Alpha-tropomyosin; Finland; beta-myosin heavy chain; cardiac myosin-binding protein C; genetics; hypertrophic cardiomyopathy
Authors: Pertti Jääskeläinen; Jagadish Vangipurapu; Joose Raivo; Teemu Kuulasmaa; Tiina Heliö; Katriina Aalto-Setälä; Maija Kaartinen; Erkki Ilveskoski; Sari Vanninen; Liisa Hämäläinen; John Melin; Jorma Kokkonen; Markku S Nieminen; Markku Laakso; Johanna Kuusisto Journal: ESC Heart Fail Date: 2019-02-18
Authors: I H M van der Linde; Y L Hiemstra; R Bökenkamp; A M van Mil; M H Breuning; C Ruivenkamp; S W Ten Broeke; R F Veldkamp; J I van Waning; M A van Slegtenhorst; K Y van Spaendonck-Zwarts; R H Lekanne Deprez; J C Herkert; L Boven; P A van der Zwaag; J D H Jongbloed; M Bootsma; D Q C M Barge-Schaapveld Journal: Neth Heart J Date: 2017-09-01 Impact factor: 2.380