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Die genetischen Ursachen der hypertrophischen Kardiomyopathie

Genetic causes of hypertrophic cardiomyopathy

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Zusammenfassung

□ Die hypertrophische Kardiomyopathie ist eine dominant vererbte Erkrankung des Myokards. Die bisher identifizierten Ursachen erfassen bis zu 75% aller Fälle. Die für die Krankheit verantwortlichen Mutationen führen zu Veränderungen von Proteinen, die eine myokardiale „Motorfunktion” haben oder die diese funktion kontrollieren. Die hypertrophische Kardiomyopathie kann deshalb als eine Krankheit des myokardialen Muskelapparates definiert werden.

□ Die klinische Progression ist langsam. Das größte Risiko dieser Krankheit ist der plötzliche Herztod. Im Gegensatz zu den Ursachen ist die Pathogenese der hypertrophischen Kardiomyopathie noch nicht geklärt.

Summary

□ Hypertrophic cardiomyopathy is a dominantly inherited disease of the heart. Heterogeneous sets of mutations responsible for this condition have been identified in seven genes coding for proteins involved in the contraction mechanism or in the control of contraction of the myocardium. Known mutations imply structural and functional changes in the following proteins: in ventricle specific β-myosin heavy chain, in essential and regulatory myosin light chains, in troponin subunits T and I, in α-tropomyosin and in myosin binding protein-C. The gene of one additional genomic HCM-locus is not known. Since two thirds or more of all cases can be traced to one of the respective genes, HCM has been classified as a disease of the cardiac sarcomere. Heterogeneity does not only exist between genes, but also within genes. At least 84 different mutations have been identified to date. More than half of them have been detected in the β-myosin heavy chain gene. Thus, mutations in this gene account for most of the cases of HCM. The extent of data about causes is in contrast to the lack of definite knowledee about pathogenic mechanisms. Since the disorder is in many cases mild with symptoms developing frequently not before the end of the second decade, myocardial dysfunctions can presumably not directly be traced to altered contractility, but rather to effects which accumulate with a long asymptomatic lag period and which gradually lead to hypertrophy, conduction problems and ultimately to cardiac failure. The disease may be considered as an indirect and secondary response to a mildly distorted contraction process. The rapid progress in the analysis of causes suggests that the study of genes will assume a role in the context of the clinical management of HCM, in particular regarding diagnosis, prognosis, counselling of patients and families and -possibly-therapy.

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  1. Abteilung Experimentelle Kardiologie, Max-Planck-Institut für physiologische und klinische Forschung, Benekestraße 2, D-61231, Bad Nautheim

    Hans -Peter Vosberg

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Vosberg, H.P. Die genetischen Ursachen der hypertrophischen Kardiomyopathie. Med Klin 93, 252–259 (1998). https://doi.org/10.1007/BF03044801

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