title: Prognostic predictive value of gene mutations in Japanese patients with hypertrophic cardiomyopathy.
abstract: Although some studies have attempted to find useful prognostic factors in hypertrophic cardiomyopathy (HCM), those results are not fully helpful for use in actual clinical practice. Furthermore, several genetic abnormalities associated with HCM have been identified. However, the genotype-phenotype correlation in HCM remains to be elucidated. Here, we attempted to assess patients with different types of gene mutations causing HCM and investigate the prognosis. A total of 140 patients with HCM underwent a screening test for myofilament gene mutations by direct sequencing of eight sarcomeric genes. Patients with a single mutation in cardiac troponin T, cardiac troponin I, α-tropomyosin, and regulatory and essential light chains were excluded from the study because the number of cases was too small. The clinical presentations and outcomes of the remaining 127 patients with HCM, 31 β-myosin heavy chain (MYH7) mutation carriers, 19 cardiac myosin-binding protein C (MYBPC3) mutation carriers, and 77 mutation non-carriers were analyzed retrospectively. MYBPC3 mutation carriers had a high frequency of ventricular arrhythmia and syncope. Kaplan-Meier curves revealed no significant difference in prognosis among the three groups, but a lack of family history of sudden death (SD) and a past history of syncope were significantly related to poor prognosis. An absence of family history of SD and past history of syncope are useful prognostic factors in patients with HCM. MYH7 and MYBPC3 mutations did not significantly influence prognosis compared to non-carriers. However, patients with the MYBPC3 mutation should be closely followed for the possibility of SD.
authors.affiliation: Department of Pediatrics, National Defense Medical College, Tokorozawa, Japan.|Department of Pediatric Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Chida
authors.affiliation: Department of Pediatric Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Inai
authors.affiliation: Department of Preventive Medicine and Public Health, National Defense Medical College, Tokorozawa, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sato
authors.affiliation: Department of Pediatric Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Shimada
authors.affiliation: International Research and Educational Institute for Integrated Medical Sciences (IREIIMS), Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nishizawa
authors.affiliation: Department of Pediatric Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
authors.forename: Mitsuyo
authors.initials: M
authors.lastname: Shimada
authors.affiliation: Department of Pediatric Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Furutani
authors.affiliation: Department of Pediatric Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Furutani
authors.affiliation: Department of Pediatrics, National Defense Medical College, Tokorozawa, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kawamura
authors.affiliation: Department of Pediatrics, Asahikawa Medical University Hospital, Asahikawa, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Sugimoto
authors.affiliation: Department of Pediatrics, Yokohama Municipal Citizen's Hospital, Yokohama, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Ishihara
authors.affiliation: Department of Pediatrics, The Jikei University School of Medicine, Minato, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Fujiwara
authors.affiliation: Showa University Northern Yokohama Hospital Children's Medical Center, Shinagawa, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Soga
authors.affiliation: Department of General Medicine, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kawana
authors.affiliation: Department of Cardiology, Sendai Cardiovascular Center, Sendai, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Fuji
authors.affiliation: Department of Adult Congenital Heart Disease and Pediatric Cardiology, Chiba Cerebral and Cardiovascular Center, Ichihara, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tateno
authors.affiliation: Department of Pediatric Cardiology and Neonatology, Ogaki Municipal Hospital, Ogaki, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kuraishi
authors.affiliation: Department of Pediatrics, Osaka University Hospital, Suita, Japan.
authors.forename: Shigetoyo
authors.initials: S
authors.lastname: Kogaki
authors.affiliation: Department of Cardiology, Social Medical Corporation Bokoi Tenshi Hospital, Sapporo, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Nishimura
authors.affiliation: Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ayusawa
authors.affiliation: Department of Pediatrics, University of Toyama Hospital, Toyama, Japan.
authors.forename: Fukiko
authors.initials: F
authors.lastname: Ichida
authors.affiliation: Department of Pediatrics, Hokkaido University Hospital, Hokkaido, Japan.
authors.forename: Hirokuni
authors.initials: H
authors.lastname: Yamazawa
authors.affiliation: International Research and Educational Institute for Integrated Medical Sciences (IREIIMS), Tokyo Women's Medical University, Tokyo, Japan.|International Center for Molecular, Cellular and Immunological Research (IMCIR), Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Rumiko
authors.initials: R
authors.lastname: Matsuoka
authors.affiliation: Department of Pediatrics, National Defense Medical College, Tokorozawa, Japan.
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Nonoyama
authors.affiliation: Department of Pediatric Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan. pnakanis@hij.twmu.ac.jp.
authors.forename: Toshio
authors.initials: T
authors.lastname: Nakanishi
mesh_terms: D000293:Adolescent; D000328:Adult; D024722:Cardiac Myosins / Q000235:genetics*; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics* / Q000401:mortality*; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D016757:Death, Sudden, Cardiac / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D007564:Japan; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011237:Predictive Value of Tests; D012044:Regression Analysis; D055815:Young Adult; D000099163:Myosin Binding Protein C
chemical_list: D024722:Cardiac Myosins; D002352:Carrier Proteins; D018995:Myosin Heavy Chains; D000099163:Myosin Binding Protein C; C501641:MYH7 protein, human
keywords: Gene mutation; Genotype–phenotype; HCM; Prognosis