1. Genetic basis and outcome in a nationwide study of Finnish patients with hypertrophic cardiomyopathy
- Author
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Helena Kervinen, Paavo Uusimaa, Juhani Junttila, Tiina Heliö, Mari Niemi, Joose Raivo, Maija Kaartinen, John Melin, Ilkka Mahonen, Markku Laakso, Johanna Kuusisto, Liisa Hämäläinen, Heini Jyrkila, Matti Kotila, Paula Vartia, Markku S. Nieminen, Erkki Ilveskoski, Mikko Pietilä, Teemu Kuulasmaa, Jukka Juvonen, Pertti Jääskeläinen, FinHCM Study Grp, Jagadish Vangipurapu, Juha Mustonen, Sari U. M. Vanninen, Jorma Kokkonen, Katriina Aalto-Setälä, Department of Medicine, Clinicum, Kardiologian yksikkö, and HUS Heart and Lung Center
- Subjects
Male ,medicine.medical_treatment ,DNA Mutational Analysis ,ASP175ASN MUTATION ,TPM1 ,030204 cardiovascular system & hematology ,DISEASE ,0302 clinical medicine ,FOUNDER MUTATIONS ,Original Research Articles ,MAGNETIC-RESONANCE ,Original Research Article ,Registries ,030212 general & internal medicine ,Finland ,Outcome ,education.field_of_study ,Hazard ratio ,Hypertrophic cardiomyopathy ,IMPAIRMENT ,Implantable cardioverter-defibrillator ,Pedigree ,3. Good health ,Survival Rate ,INSIGHTS ,Targeted sequencing ,cardiovascular system ,Female ,Cardiology and Cardiovascular Medicine ,Sarcomeres ,Heterozygote ,medicine.medical_specialty ,Population ,03 medical and health sciences ,ALPHA-TROPOMYOSIN ,Internal medicine ,Genetics ,medicine ,Humans ,cardiovascular diseases ,education ,business.industry ,MORTALITY ,Cardiomyopathy, Hypertrophic ,medicine.disease ,Confidence interval ,HEAVY-CHAIN GENE ,3121 General medicine, internal medicine and other clinical medicine ,Heart failure ,Mutation ,MYH7 ,business ,Cardiac Myosins ,Follow-Up Studies ,Forecasting - Abstract
Aims Nationwide large-scale genetic and outcome studies in cohorts with hypertrophic cardiomyopathy (HCM) have not been previously published. Methods and results We sequenced 59 cardiomyopathy-associated genes in 382 unrelated Finnish patients with HCM and found 24 pathogenic or likely pathogenic mutations in six genes in 38.2% of patients. Most mutations were located in sarcomere genes (MYBPC3, MYH7, TPM1, and MYL2). Previously reported mutations by our study group (MYBPC3-Gln1061Ter, MYH7-Arg1053Gln, and TPM1-Asp175Asn) and a fourth major mutation MYH7-Val606Met accounted for 28.0% of cases. Mutations in GLA and PRKAG2 were found in three patients. Furthermore, we found 49 variants of unknown significance in 31 genes in 20.4% of cases. During a 6.7 +/- 4.2 year follow-up, annual all-cause mortality in 482 index patients and their relatives with HCM was higher than that in the matched Finnish population (1.70 vs. 0.87%; P
- Published
- 2019