It has been demonstrated previously that clinical phenotypes of HCM (hypertrophic cardiomyopathy) caused by mutations in the cardiac MyBP-C (myosin-binding protein C) gene show late onset, low penetrance and favourable clinical course. However, we have encountered severe phenotypes in several carriers of the MyBP-C gene mutations. The aim of the present study was to screen novel MyBP-C gene mutations in patients with HCM and to investigate the genetic differences in affected subjects with severe phenotypes. The MyBP-C gene was screened in 292 Japanese probands with HCM, and a novel c.2067+1G→A mutation was present in 15 subjects in five families. Clinical phenotypes of carriers of the c.2067+1G→A mutation were compared with those of a previously identified Arg820Gln (Arg820→Gln) mutation in the MyBP-C gene. The disease penetrance in subjects aged ≥30 years was 90% in carriers of the c.2067+1G→A mutation and 61% in carriers of the Arg820Gln mutation. Sudden death occurred in four subjects from three families with the c.2067+1G→A mutation and in two subjects from one family with the Arg820Gln mutation. Two carriers of the c.2067+1G→A mutation had substantial hypertrophy (maximal wall thickness ≥30 mm). In contrast, two carriers of the Arg820Gln mutation had end-stage HCM. In conclusion, the c.2067+1G→A mutation is associated with HCM with substantial hypertrophy and moderate incidence of sudden death, whereas the Arg820Gln mutation is associated with end-stage HCM. These observations may provide important prognostic information regarding the clinical practice of HCM.
A novel mutation in the cardiac myosin-binding protein C gene is responsible for hypertrophic cardiomyopathy with severe ventricular hypertrophy and sudden death
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Tetsuo Konno, Masami Shimizu, Hidekazu Ino, Noboru Fujino, Katsuharu Uchiyama, Tomohito Mabuchi, Kenji Sakata, Tomoya Kaneda, Takashi Fujita, Eiichi Masuta, Hiroshi Mabuchi; A novel mutation in the cardiac myosin-binding protein C gene is responsible for hypertrophic cardiomyopathy with severe ventricular hypertrophy and sudden death. Clin Sci (Lond) 1 January 2006; 110 (1): 125–131. doi: https://doi.org/10.1042/CS20050189
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