Mutation Causes Heart Muscle Disorder - Researchers in Berlin und Boston Detect Genetic Defect

05-Dec-2006

A mutation in a gene responsible for the adhesion of adjacent cells of the heart is the cause of a potentially lethal heart muscle disorder. The evidence has been provided by a team of researchers including Dr. Arnd Heuser of the Max Delbrück Center of Molecular medicine (MDC) Berlin-Buch, Germany, Dr. Eva R. Plovie of the Massachusetts General Hospital (MGH) in Boston, USA, and Professor Ludwig Thierfelder (MDC and Helios Klinikum Berlin/Charité) and Dr. Brenda Gerull (MDC). The scientists searched selectively mutations in the gene Desmocollin-2 (DSC2) in a pool of 88 unrelated patients suffering from arrhythmogenic right ventricular cardiomyopathy (ARVC) and discovered a mutation that causes this cardiomyopathy. By switching off the gene in zebrafish embryos, they demonstrated that DSC2 is essential for normal mycardial structure and function.

In collaboration with researchers from the University Hospital of Münster, Dr. Heuser (MDC) and Dr. Plovie (MGH) searched for genetic defects in the desmosomes within a pool of 88 unrelated patients. Desmosomes are mechanical structures that keep the cells bound together as if connected with push buttons so that they will not rip while beating. They searched for a mutation in the gene that carries the information for the protein Desmocollin-2 (DSC2) which is part of the desmosome structure. Mutations of other desmosomal proteins have previously been detected for ARVC. Therefore, the Berlin- and Boston-based researchers assumed that mutations in DSC2 could result in ARVC, too.

Dr. Heuser and Dr. Plovie could now demonstrate that the mutation in DSC2 gene results in a reduced DSC2 protein which causes ARVC. Furthermore, the switch off of the DSC2 in zebrafish embryos showed that DSC2 is necessary for normal embryonic cardiac development. In an adult organism, a lack of DSC2 leads to disordered heart contraction and difficulties in the conduction system of the heart.

Original publication: Arnd Heuser, Eva R. Plovie, Patrick T. Ellinor, Katja S. Grossmann, Jordan T. Shin, Thomas Wichter, Craig T. Basson, Bruce B. Lerman, Sabine Sasse-Klaassen, Ludwig Thierfelder, Calum A. MacRae, Brenda Gerull; "Mutant Desmocollin-2 Causes Arrhythmogenic Right Ventricular Cardiomyopathy"; American Journal of Human Genetics 2006, Vol. 79, pp. 1081-1088.

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