The cardiac β-myosin heavy chain gene is not the predominant gene for hypertrophic cardiomyopathy in the Finnish population

被引:55
作者
Jääskeläinen, P
Soranta, M
Miettinen, R
Saarinen, L
Pihlajamäki, J
Silvennoinen, K
Tikanoja, T
Laakso, M
Kuusisto, J
机构
[1] Univ Kuopio, Dept Med, SF-70210 Kuopio, Finland
[2] Natl Inst Publ Hlth, Div Environm Hlth, Kuopio, Finland
[3] Univ Kuopio, Dept Pediat, Kuopio, Finland
基金
芬兰科学院;
关键词
D O I
10.1016/S0735-1097(98)00448-3
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objectives. The aim of the study was to screen 36 unrelated patients with hypertrophic cardiomyopathy (HCM; 16 familial and 20 sporadic cases) from a genetically homogeneous area in eastern Finland for variants in the cardiac beta-myosin heavy chain (beta-MHC) and alpha-tropomyosin (alpha-TM) genes. Background. Mutations in the beta-MHC and alpha-TM genes have been reported to be responsible for 30% to 40% and less than 5% of familial HCM cases, respectively. However, most genetic studies have included patients from tertiary care centers and are subject to referral bias. Methods. Exons 3-26 and 40 of the beta-MHC gene and the nine exons of the alpha-TM gene were screened with the PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism) method. Linkage analyses between familial HCM locus and two intragenic polymorphic markers (MYO I and MYO II) of the beta-MHC gene were performed in 16 familial HCM kindreds. Results. A previously reported Arg719Trp (arginine converted to tryptophan in codon 719) mutation of the beta-MHC gene was found in one proband and two relatives. In addition, a novel Asn696Ser (asparagine converted to serine in codon 696) substitution was found in one HCM patient. No linkage between familial HCM and the beta-MHC gene was observed in 16 familial kindreds. A previously reported Asp175Asn (aspartic acid converted to asparagine in codon 175) mutation of the alpha-TM gene was found in four probands and 16 relatives. Mutations in the beta-MHC and alpha-TM genes accounted for 6% and 25% familial HCM cases and 3% and 11% of all cases, respectively. Conclusions. Our results indicate that the beta-MBC gene is not the predominant gene for HCM in the Finnish population, whereas HCM caused by the Asp175Asn mutation of the alpha-TM gene is more common than previously reported. (J Am Cell Cardiol 1998;32:1709-16) (C) 1998 by the American College of Cardiology.
引用
收藏
页码:1709 / 1716
页数:8
相关论文
共 36 条
[1]   CARDIAC MYOSIN BINDING PROTEIN-C GENE SPLICE ACCEPTOR SITE MUTATION IS ASSOCIATED WITH FAMILIAL HYPERTROPHIC CARDIOMYOPATHY [J].
BONNE, G ;
CARRIER, L ;
BERCOVICI, J ;
CRUAUD, C ;
RICHARD, P ;
HAINQUE, B ;
GAUTEL, M ;
LABEIT, S ;
JAMES, M ;
BECKMANN, J ;
WEISSENBACH, J ;
VOSBERG, HP ;
FISZMAN, M ;
KOMAJDA, M ;
SCHWARTZ, K .
NATURE GENETICS, 1995, 11 (04) :438-440
[2]   Clinical features of hypertrophic cardiomyopathy caused by mutation of a ''hot spot'' in the alpha-tropomyosin gene [J].
Coviello, DA ;
Maron, BJ ;
Spirito, P ;
Watkins, H ;
Vosberg, HP ;
Thierfelder, L ;
Schoen, FJ ;
Seidman, JG ;
Seidman, CE .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 1997, 29 (03) :635-640
[3]   DISEASE GENE-MAPPING IN ISOLATED HUMAN-POPULATIONS - THE EXAMPLE OF FINLAND [J].
DELACHAPELLE, A .
JOURNAL OF MEDICAL GENETICS, 1993, 30 (10) :857-865
[4]   A MOLECULAR-BASIS FOR FAMILIAL HYPERTROPHIC CARDIOMYOPATHY - A BETA-CARDIAC MYOSIN HEAVY-CHAIN GENE MISSENSE MUTATION [J].
GEISTERFERLOWRANCE, AAT ;
KASS, S ;
TANIGAWA, G ;
VOSBERG, HP ;
MCKENNA, W ;
SEIDMAN, CE ;
SEIDMAN, JG .
CELL, 1990, 62 (05) :999-1006
[5]  
HUWEZ FU, 1994, BRIT HEART J, V72, P276
[6]   THE COMPLETE SEQUENCE OF THE HUMAN BETA-MYOSIN HEAVY-CHAIN GENE AND A COMPARATIVE-ANALYSIS OF ITS PRODUCT [J].
JAENICKE, T ;
DIEDERICH, KW ;
HAAS, W ;
SCHLEICH, J ;
LICHTER, P ;
PFORDT, M ;
BACH, A ;
VOSBERG, HP .
GENOMICS, 1990, 8 (02) :194-206
[7]   Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy [J].
Kimura, A ;
Harada, H ;
Park, JE ;
Nishi, H ;
Satoh, M ;
Takahashi, M ;
Hiroi, S ;
Sasaoka, T ;
Ohbuchi, N ;
Nakamura, T ;
Koyanagi, T ;
Hwang, TH ;
Choo, TA ;
Chung, KS ;
Hasegawa, A ;
Nagai, R ;
Okazaki, O ;
Nakamura, H ;
Matsuzaki, M ;
Sakamoto, T ;
Toshima, H ;
Koga, Y ;
Imaizumi, T ;
Sasazuki, T .
NATURE GENETICS, 1997, 16 (04) :379-382
[8]   DIRECT SEQUENCING FROM LOW-MELT AGAROSE WITH SEQUENASE [J].
KRETZ, KA ;
CARSON, GS ;
OBRIEN, JS .
NUCLEIC ACIDS RESEARCH, 1989, 17 (14) :5864-5864
[9]   INSULIN-RECEPTOR SUBSTRATE-1 VARIANTS IN NON-INSULIN-DEPENDENT DIABETES [J].
LAAKSO, M ;
MALKKI, M ;
KEKALAINEN, P ;
KUUSISTO, J ;
DEEB, SS .
JOURNAL OF CLINICAL INVESTIGATION, 1994, 94 (03) :1141-1146
[10]  
LATHROP GM, 1984, AM J HUM GENET, V36, P460