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Is there a common genetic basis for all familial cardiomyopathies?
Author(s) -
Perrot Andreas,
Dietz Rainer,
Osterziel Karl Josef
Publication year - 2007
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1016/j.ejheart.2006.04.010
Subject(s) - hypertrophic cardiomyopathy , medicine , dilated cardiomyopathy , cardiomyopathy , coronary artery disease , population , cardiology , disease , heart failure , environmental health
According to the 1995 World Health Organization definition, cardiomyopathies are bdiseases of the myocardium associated with cardiac dysfunctionQ [1]. Traditionally, cardiomyopathies are differentiated according to the pathologic changes in cardiac morphology and function using cardiac imaging and invasive methods to exclude coronary artery disease. The two distinct patterns of cardiac remodelling, hypertrophy and dilation, are the main criteria for classifying a patient’s disease as a hypertrophic or a dilated cardiomyopathy; cardiac filling is used to define restrictive cardiomyopathy. For the practicing physician, hypertrophic (HCM), dilated (DCM), and restrictive cardiomyopathy (RCM) are clearly distinct disorders. The birth of modern cardiomyopathy research is pegged to the 1989 publication defining the first genetic locus for familial HCM on chromosome 14q1 [2]. In the following years, a knowledge explosion took place regarding new disease genes and mutations as well as the production of gene-targeted animal models (for review see [3,4]). The field received an additional boost from the completion of the human genome project and refined genetic maps, as well as the rapid progress in transgenic technologies. Whereas HCM is regarded now as a inherited monogenic disease [3], familial DCM may occur in about 20% to 50% of idiopathic cases (dependent on study population as well as criteria and clinical methods used) [5]. Due to this fact and the earlier identification of HCM disease genes, the number of known mutations is much higher in familial HCM compared to familial DCM (as also shown for three selected genes in Fig. 2). The genetic results of most studies underscored the differences in familial cardiomyopathies. It was shown that mutations in genes encoding for sarcomeric proteins of the thin and thick filaments exclusively cause familial HCM while mutations in genes encoding for cytoskelatal proteins cause familial DCM. As a result, the overall picture seemed well structured and conclusive. However, the bfunnyQ thing is that reality is more complex than our perceptions. Recent studies changed our