Familial Hypertrophic Cardiomyopathy
- 21 September 1998
- journal article
- review article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation Research
- Vol. 83 (6), 580-593
- https://doi.org/10.1161/01.res.83.6.580
Abstract
Hypertrophic cardiomyopathy is characterized by left and/or right ventricular hypertrophy, which is usually asymmetric and involves the interventricular septum. Typical morphological changes include myocyte hypertrophy and disarray surrounding the areas of increased loose connective tissue. Arrhythmias and premature sudden deaths are common. Hypertrophic cardiomyopathy is familial in the majority of cases and is transmitted as an autosomal-dominant trait. The results of molecular genetics studies have shown that familial hypertrophic cardiomyopathy is a disease of the sarcomere involving mutations in 7 different genes encoding proteins of the myofibrillar apparatus: ss-myosin heavy chain, ventricular myosin essential light chain, ventricular myosin regulatory light chain, cardiac troponin T, cardiac troponin I, alpha-tropomyosin, and cardiac myosin binding protein C. In addition to this locus heterogeneity, there is a wide allelic heterogeneity, since numerous mutations have been found in all these genes. The recent development of animal models and of in vitro analyses have allowed a better understanding of the pathophysiological mechanisms associated with familial hypertrophic cardiomyopathy. One can thus tentatively draw the following cascade of events: The mutation leads to a poison polypeptide that would be incorporated into the sarcomere. This would alter the sarcomeric function that would result (1) in an altered cardiac function and then (2) in the alteration of the sarcomeric and myocyte structure. Some mutations induce functional impairment and support the pathogenesis hypothesis of a "hypocontractile" state followed by compensatory hypertrophy. Other mutations induce cardiac hyperfunction and determine a "hypercontractile" state that would directly induce cardiac hypertrophy. The development of other animal models and of other mechanistic studies linking the genetic mutation to functional defects are now key issues in understanding how alterations in the basic contractile unit of the cardiomyocyte alter the phenotype and the function of the heart.Keywords
This publication has 97 references indexed in Scilit:
- Effects of Two Hypertrophic Cardiomyopathy Mutations in α-Tropomyosin, Asp175Asn and Glu180Gly, on Ca2+Regulation of Thin Filament MotilityBiochemical and Biophysical Research Communications, 1997
- Angiotensin-converting enzyme gene polymorphism in Japanese patients with hypertrophic cardiomyopathyAmerican Heart Journal, 1995
- Possible Gene Effect of a Mutant Cardiac β-Myosin Heavy Chain Gene on the Clinical Expression of Familial Hypertrophic CardiomyopathyBiochemical and Biophysical Research Communications, 1994
- A Missense Mutation of Cardiac β-Myosin Heavy Chain Gene Linked to Familial Hypertrophic Cardiomyopathy in Affected Japanese FamiliesBiochemical and Biophysical Research Communications, 1993
- Complete nucleotide sequence and structural organization of rat cardiac troponin T geneJournal of Molecular Biology, 1992
- Drosophila melanogaster troponin-T mutations engender three distinct syndromes of myofibrillar abnormalitiesJournal of Molecular Biology, 1990
- Mapping a Gene for Familial Hypertrophic Cardiomyopathy to Chromosome 14q1New England Journal of Medicine, 1989
- Hypertrophic CardiomyopathyNew England Journal of Medicine, 1987
- Heart C-protein is transiently expressed during skeletal muscle development in the embryo, but persists in cultured myogenic cellsDevelopmental Biology, 1985
- The light chains of scallop myosin as regulatory subunitsJournal of Molecular Biology, 1973