What makes the heart fail? New insights from defective genes.
Dilated cardiomyopathy (DCM) is an idiopathic, genetically heterogeneous disorder characterized by heart failure and arrhythmia. Over the past decade, the molecular basis for DCM has been partially uncovered by discovery of mutation in genes encoding cystoskeletal, sarcomeric, nuclear membrane, and sarcoplasmic reticulum proteins. These findings have implicated pathogenic mechanisms whereby structural integrity, contractile force dynamics, and calcium regulation within the cardiac myocyte are perturbed. Recognition of dilated and hypertrophic cardiomyopathies as allelic disorders has provided the opportunity to identify genotype-phenotype relationships and to gain new insight into pathways leading to cardiac failure and hypertrophy.


CONCLUSIONS
Collectively, family-based studies of DCM provide the rationale for clinical screening in first-degree relatives, regardless of family history or age of the index case.
Olson
Timothy M
TM
Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA. olson.timothy@mayo.edu
D000199:Actins / Q000235:genetics; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000503:physiopathology; D003598:Cytoskeletal Proteins / Q000235:genetics; D004252:DNA Mutational Analysis; D008040:Genetic Linkage; D006801:Humans; D020125:Mutation, Missense; D009200:Myocardial Contraction / Q000235:genetics; D032383:Myocytes, Cardiac / Q000502:physiology
D000199:Actins; D003598:Cytoskeletal Proteins