title: Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy.
abstract: Hypertrophic cardiomyopathy (HCM), the most common cause of sudden death in the young, is an autosomal dominant disease characterized by ventricular hypertrophy accompanied by myofibrillar disarrays. Linkage studies and candidate-gene approaches have demonstrated that about half of the patients have mutations in one of six disease genes: cardiac beta-myosin heavy chain (c beta MHC), cardiac troponin T (cTnT), alpha-tropomyosin (alpha TM), cardiac myosin binding protein C (cMBPC), ventricular myosin essential light chain (vMLC1) and ventricular myosin regulatory light chain (vMLC2) genes. Other disease genes remain unknown. Because all the known disease genes encode major contractile elements in cardiac muscle, we have systematically characterized the cardiac sarcomere genes, including cardiac troponin I (cTnI), cardiac actin (cACT) and cardiac troponin C (cTnC) in 184 unrelated patients with HCM and found mutations in the cTnI gene in several patients. Family studies showed that an Arg145Gly mutation was linked to HCM and a Lys206Gln mutation had occurred de novo, thus strongly suggesting that cTnI is the seventh HCM gene.
authors.affiliation: Department of Tissue Physiology, Tokyo Medical and Dental University, Japan. akinori.tis@cmn.tmd.ac.jp
authors.forename: A
authors.initials: A
authors.lastname: Kimura
authors.forename: H
authors.initials: H
authors.lastname: Harada
authors.forename: J E
authors.initials: JE
authors.lastname: Park
authors.forename: H
authors.initials: H
authors.lastname: Nishi
authors.forename: M
authors.initials: M
authors.lastname: Satoh
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: S
authors.initials: S
authors.lastname: Hiroi
authors.forename: T
authors.initials: T
authors.lastname: Sasaoka
authors.forename: N
authors.initials: N
authors.lastname: Ohbuchi
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: T
authors.initials: T
authors.lastname: Koyanagi
authors.forename: T H
authors.initials: TH
authors.lastname: Hwang
authors.forename: J A
authors.initials: JA
authors.lastname: Choo
authors.forename: K S
authors.initials: KS
authors.lastname: Chung
authors.forename: A
authors.initials: A
authors.lastname: Hasegawa
authors.forename: R
authors.initials: R
authors.lastname: Nagai
authors.forename: O
authors.initials: O
authors.lastname: Okazaki
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
authors.forename: M
authors.initials: M
authors.lastname: Matsuzaki
authors.forename: T
authors.initials: T
authors.lastname: Sakamoto
authors.forename: H
authors.initials: H
authors.lastname: Toshima
authors.forename: Y
authors.initials: Y
authors.lastname: Koga
authors.forename: T
authors.initials: T
authors.lastname: Imaizumi
authors.forename: T
authors.initials: T
authors.lastname: Sasazuki
mesh_terms: D000199:Actins / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine; D001483:Base Sequence; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D018076:DNA, Complementary; D005091:Exons; D005260:Female; D008040:Genetic Linkage; D005998:Glycine; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009206:Myocardium / Q000378:metabolism; D010375:Pedigree; D011110:Polymorphism, Genetic; D019209:Troponin C / Q000235:genetics; D019210:Troponin I / Q000235:genetics*; D000099163:Myosin Binding Protein C
chemical_list: D000199:Actins; D001120:Arginine; D002352:Carrier Proteins; D018076:DNA, Complementary; D005998:Glycine; D019209:Troponin C; D019210:Troponin I; D000099163:Myosin Binding Protein C