title: A novel mutation in the cardiac myosin-binding protein C gene is responsible for hypertrophic cardiomyopathy with severe ventricular hypertrophy and sudden death.
abstract: 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 > or =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 > or =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.
authors.affiliation: Molecular Genetics of Cardiovascular Disorders, Division of Cardiovascular Medicine, Graduate School of Medical Science, Kanazawa University, Takara-machi 13-1, Kanazawa 920-8640, Japan. kontetsu@im2.m.kanazawa-u.ac.jp
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Konno
authors.forename: Masami
authors.initials: M
authors.lastname: Shimizu
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Ino
authors.forename: Noboru
authors.initials: N
authors.lastname: Fujino
authors.forename: Katsuharu
authors.initials: K
authors.lastname: Uchiyama
authors.forename: Tomohito
authors.initials: T
authors.lastname: Mabuchi
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakata
authors.forename: Tomoya
authors.initials: T
authors.lastname: Kaneda
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujita
authors.forename: Eiichi
authors.initials: E
authors.lastname: Masuta
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mabuchi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D002312:Cardiomyopathy, Hypertrophic / Q000000981:diagnostic imaging / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D004252:DNA Mutational Analysis / Q000379:methods; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D019683:Penetrance; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D014463:Ultrasonography; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D000099163:Myosin Binding Protein C