title: Mutation of junctophilin type 2 associated with hypertrophic cardiomyopathy.
abstract: Junctophilin subtypes, designated as JPH1 approximately 4, are protein components of junctional complexes and play essential roles in cellular Ca2+ signaling in excitable cells. Knockout mice lacking the cardiac-type Jph2 die of embryonic cardiac arrest, and the mutant cardiac myocytes exhibit impaired formation of peripheral couplings and arrhythmic Ca2+ signaling caused by functional uncoupling between dihydropyridine and ryanodine receptor channels. Based on these observations, we hypothesized that mutations of JPH2 could cause human genetic cardiac diseases. Among 195 Japanese patients (148 index cases and 47 affected family members) with hypertrophic cardiomyopathy (HCM), two heterozygous nonsynonymous nucleotide transitions, G505S and R436C, were newly found in JPH2. When Fisher's exact test was used to compare index cases with HCM to unrelated Japanese healthy controls in the frequencies of mutant alleles, only the G505S mutation showed statistical significance (4/296 HCM patients and 0/472 control individuals, P=0.022). This result was still significant after Bonferroni's correction for multiple comparisons (P=0.044). To the best of our knowledge, this is the first report on JPH2 mutation associated with HCM.
authors.affiliation: International Research and Educational Institute for Integrated Medical Sciences, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.|Division of Integrated Medical Sciences, Institute of Advanced Biomedical Engineering and Science, Graduate School of Medicine, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Matsushita
authors.affiliation: International Research and Educational Institute for Integrated Medical Sciences, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.|Division of Integrated Medical Sciences, Institute of Advanced Biomedical Engineering and Science, Graduate School of Medicine, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Furukawa
authors.affiliation: Department of Cardiology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kasanuki
authors.affiliation: Department of Pediatrics, Kagoshima Seikyo General Hospital, Kagoshima, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nishibatake
authors.affiliation: Department of Pediatrics, St. Marianna University School of Medicine, Kawasaki, Japan.
authors.forename: Yachiyo
authors.initials: Y
authors.lastname: Kurihara
authors.affiliation: Department of Biological Chemistry, Kyoto University Graduate School of Pharmaceutical Science, Kyoto, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ikeda
authors.affiliation: Division of Genomic Medicine, Department of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
authors.affiliation: Department of Biological Chemistry, Kyoto University Graduate School of Pharmaceutical Science, Kyoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeshima
authors.affiliation: International Research and Educational Institute for Integrated Medical Sciences, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan. rumiko@imcir.twmu.ac.jp.|Division of Integrated Medical Sciences, Institute of Advanced Biomedical Engineering and Science, Graduate School of Medicine, Tokyo Women's Medical University, Tokyo, Japan. rumiko@imcir.twmu.ac.jp.|Division of Pediatric Cardiology, Tokyo Women's Medical University, Tokyo, Japan. rumiko@imcir.twmu.ac.jp.
authors.forename: Rumiko
authors.initials: R
authors.lastname: Matsuoka
mesh_terms: D020013:Calcium Signaling; D002312:Cardiomyopathy, Hypertrophic / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation
chemical_list: D008565:Membrane Proteins; C412507:junctophilin