Clinical Research Group Cardiomyopathy
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Molecular research / CardioGenetic Lab
Andreas Perrot, Dipl.-Ing. Biotech., and Prof. Dr. med. K. J. Osterziel
After obtaining informed consent according to the ethical commission of the University Hospital Charit� the clinical data (family history, ECG, holter-ECG, Echo and heart catherization) of patients with Hypertrophic and Dilated Cardiomyopathy are evaluated and registered in the database CMP developed by us. These well phenotyped patients (from Berlin and other cooperating centers in Germany and other countries) are the basis for our scientific studies. Until October 2003 we have collected a group of more than 400 index patients with Hypertrophic Cardiomyopathy (HCM) and more than 500 index patients with Dilated Cardiomyopathy (DCM).
We are analysing DNA of HCM and DCM patients and looking for mutations in disease genes and further candidate genes (in cooperation with the Institute of Laboratory Medicine and Biochemistry/Charit� Campus Virchow Clinic). Analysis is mainly done with single strand conformation polymorphism analysis (SSCP) of all PCR amplified exons of the gene and automated sequencing. Several mutations (missense mutations, deletions, and insertions) in different genes (e.g. myosin heavy chain, myosin binding protein C, regulatory myosin light chain, a-actin etc) were identified. Recently, we were able to identify a new HCM disease gene, the muscle LIM protein (MLP) gene.
Beside causal mutations we are interested to identify genetic modifiers for cardiomyopathies. The role of genetic polymorphisms (e.g. in genes of the endothelin and the renin angiotension system) is analysed in different association studies (case/control studies) with well defined groups of unrelated individuals.
Linkage analysis is done in families using a panel of highly polymorphic microsattelites (in close cooperation with Gene Mapping Center/Max Delbr�ck Center for Molecular Medicine). We were able to describe the first locus for DCM in a german family. After exclusion of known loci, we performed a genome screen and detected linkage of DCM to chromosome 2q14-q22.
Studies concerning mutation and function are done in collaboration with the department of Molecular and Cellular Physiology/ Medical School Hannover. Muscle fibers from genotyped patients were analysed, e.g. for alterations in calcium sensitivity.
Further, the expression of genes in myocardial tissue of patients with cardiomyopathies is analysed. The goal of this project is to generate gene expression profiles from normal versus diseased heart tissues, as a basis to increase the understanding of the genes involved in these diseases, thereby assisting in the development of new diagnostic and therapeutic strategies.