STATE-OF-THE-ART PAPER
The Genetic Bases of Cardiomyopathies
Pascale Richard, MD, PhD , ,
Eric Villard, PhD||,
Philippe Charron, MD, PhD*, ,|| and
Richard Isnard, MD*,,*
* Institut de Cardiologie
Fédération de Biochimie, Unité Fonctionnelle de Cardiogénétique et Myogénétique
Département de Génétique
INSERM U 582
|| INSERM U621, Centre Hospitalo-Universitaire Pitié-Salpêtrière, Université Pierre et Marie Curie, Paris, France
Manuscript received August 4, 2006;
revised manuscript received September 15, 2006,
accepted September 15, 2006.
* Reprint requests and correspondence: Dr. Richard Isnard, Institut de Cardiologie, Centre Hospitalo-Universitaire Pitié-Salpêtrière, 47-83 Boulevard de l'Hôpital, 75651 Paris Cedex 13, France. (Email: richard.isnard{at}psl.aphp.fr).
Cardiomyopathies represent an important cause of cardiovascular morbidity and mortality due to heart failure, arrhythmias, and sudden death. A majority of hypertrophic cardiomyopathies (HCM) and at least 30% of dilated cardiomyopathies (DCM) are familial forms, with most often an autosomal dominant mode of inheritance. Over the last 15 years, our knowledge on the genetic bases of these diseases has considerably improved. Cardiomyopathies are characterized by a great genetic heterogeneity at both allelic and non-allelic levels. Hypertrophic cardiomyopathies are mainly linked to mutations on genes encoding sarcomeric proteins, and beta myosin heavy chain and myosin binding protein C gene mutations account for about 80% of genotyped cases. Familial DCM is associated with mutations in genes encoding sarcomeric proteins but also other proteins of the myocyte, such as cytoskeletal or nuclear membrane proteins. Due to the genetic heterogeneity and the variable clinical expressivity of these diseases, the relations between genotype and phenotype remain complex, but the age of onset, the clinical severity, or associated phenotypes may be, at least in part, related to the precise gene mutations. Therefore, besides a better understanding of the molecular basis for cardiac remodeling and heart failure, the genetic analysis of cardiomyopathies is going to play an increasing role in the routine management of these patients in the following years, particularly in HCM.
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Abbreviations and Acronyms
| | ATP = adenosine triphosphate | | DCM = dilated cardiomyopathy | | HCM = hypertrophic cardiomyopathy | | LVH = left ventricular hypertrophy |
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