Idiopathic restrictive cardiomyopathy is part of the clinical expression of cardiac troponin I mutations

被引:253
作者
Mogensen, J
Kubo, T
Duque, M
Uribe, W
Shaw, A
Murphy, R
Gimeno, JR
Elliott, P
McKenna, WJ
机构
[1] St George Hosp, Sch Med, Dept Cardiol Sci, London SW17 0RE, England
[2] Kochi Med Sch, Dept Med & Geriatr, Kochi, Japan
[3] Clin Medellin, Dept Cardiol, Medellin, Colombia
关键词
D O I
10.1172/JCI200316336
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Restrictive cardiomyopathy (RCM) is an uncommon heart muscle disorder characterized by impaired filling of the ventricles with reduced volume in the presence of normal or near normal wall thickness and systolic function. The disease may be associated with systemic disease but is most often idiopathic. We recognized a large family in which individuals were affected by either idiopathic RCM or hypertrophic cardiomyopathy (HCM). Linkage analysis to selected sarcomeric contractile protein genes identified cardiac troponin I (TNNI3) as the likely disease gene. Subsequent mutation analysis revealed a novel missense mutation, which cosegregated with the disease in the family (lod score: 4.8). To determine if idiopathic RCM is part of the clinical expression of TNNI3 mutations, genetic investigations of the gene were performed in an additional nine unrelated RCM patients with restrictive filling patterns, bi-atrial dilatation, normal systolic function, and normal wall thickness. TNNI3 mutations were identified in six of these nine RCM patients. Two of the mutations identified in young individuals were de novo mutations. All mutations appeared in conserved and functionally important domains of the gene. The identification of TNNI3 mutations in idiopathic RCM patients indicates that this phenotype is part of the spectrum of hereditary sarcomeric contractile protein disease.
引用
收藏
页码:209 / 216
页数:8
相关论文
共 32 条
[1]   Morphologic spectrum of primary restrictive cardiomyopathy [J].
Angelini, A ;
Calzolari, V ;
Thiene, G ;
Boffa, GM ;
Valente, M ;
Daliento, L ;
Basso, C ;
Calabrese, F ;
Razzolini, R ;
Livi, U ;
Chioin, R .
AMERICAN JOURNAL OF CARDIOLOGY, 1997, 80 (08) :1046-1050
[2]   Isolation and characterization of the human cardiac troponin I gene (TNNI3) [J].
Bhavsar, PK ;
Brand, NJ ;
Yacoub, MH ;
Barton, PJR .
GENOMICS, 1996, 35 (01) :11-23
[3]  
Charron P, 1997, CIRCULATION, V96, P214
[4]   Complexity in simplicity: monogenic disorders and complex cardiomyopathies [J].
Chen, J ;
Chien, KR .
JOURNAL OF CLINICAL INVESTIGATION, 1999, 103 (11) :1483-1485
[5]   Altered regulatory properties of human cardiac troponin I mutants that cause hypertrophic cardiomyopathy [J].
Elliott, K ;
Watkins, H ;
Redwood, CS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (29) :22069-22074
[6]  
FELD S, 1992, ISRAEL J MED SCI, V28, P277
[7]  
FITZPATRICK AP, 1990, BRIT HEART J, V63, P114
[8]   ECHOCARDIOGRAPHIC MEASUREMENTS IN NORMAL SUBJECTS - EVALUATION OF AN ADULT-POPULATION WITHOUT CLINICALLY APPARENT HEART-DISEASE [J].
GARDIN, JM ;
HENRY, WL ;
SAVAGE, DD ;
WARE, JH ;
BURN, C ;
BORER, JS .
JOURNAL OF CLINICAL ULTRASOUND, 1979, 7 (06) :439-447
[9]   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
[10]   ECHOCARDIOGRAPHIC MEASUREMENTS IN NORMAL SUBJECTS - GROWTH-RELATED CHANGES THAT OCCUR BETWEEN INFANCY AND EARLY ADULTHOOD [J].
HENRY, WL ;
WARE, J ;
GARDIN, JM ;
HEPNER, SI ;
MCKAY, J ;
WEINER, M .
CIRCULATION, 1978, 57 (02) :278-285