Etiology of Heart Failure - Project Description
Background
Illnesses originating primarily in cardiac muscle tissue - the cardiomyopathies - are the third most common cause of heart failure in western industrialized nations after coronary artery disease and hypertension. The most common form of cardiomyopathy is dilated cardiomyopathy (DCM), in which the cardiac cavities are enlarged and there is a loss of function. The second most common form is hypertrophic cardiomyopathy (HCM), in which the myocardial tissue thickens abnormally.
The enormous progress in the identification of disease genes have fundamentally changed our understanding of cardiomyopathies. It is well-known that mutations lead to different forms and variations in the progression of the illness. However, genetic examinations have been reserved for scientific research up to now, and thus limited to very few patients and families. For this reason, we do not have enough experience with a sufficient number of precisely genotyped patients in estimating the significance of individual mutations for the highly variable clinical progression of cardiomyopathies.
Objective
Subproject 5 has two primary goals: on the one hand, cross-linked research should enable us to offer patients with hypertrophic and dilated cardiomyopathy (HCM and DCM) molecular diagnoses. The primary focus here is on the development and validation of a molecular genetic diagnostic procedure that meets the requirements of timely, cost-effective and accurate human genetic examinations. On the other hand, these examinations should be representative and record the frequency of mutations in the known disease genes as well as their correlation to the clinical forms of heart failure.
Implementation
The starting point comprises patients with HCM and DCM nationwide who have been clinically genotyped at leading cardiological centers. For these patients a systematic search for the underlying mutations will be performed using DNA sequencing. In patients with positive genetic findings, a follow-up examination will be carried out, and a family-oriented examination targeted. The data generated as part of the genetic testing will be used for the clinical testing of a microarray for HCM. If this so-called HCM chip is successful, a validated, uniform method for human genetic testing of HCM patients would be available throughout Germany for the first time.
Added value via networking
The networking of leading university and non-university cardiological centers and genetic laboratories facilitated for the first time the comprehensive clinical and genetic characterization of a large group of HCM and DCM patients nationwide. Thus it is possible to generate results regarding the type and frequency of mutations as well as their specific clinical manifestations with a high degree of scientific accuracy. Genetic testing for HCM and DCM are still very labor-intensive and time-consuming and are offered only by a few laboratories according to individual standards. The collaboration of molecular genetic laboratories in subproject 5 facilitates the creation of a range of diagnostic procedures for affected persons according to uniform standards. There is also collaboration with work groups of the German National Genome Research Network (NGFN). The collaboration with other projects of the competence network on the basis of patient recruitment and centralized data and sample recording is crucial to the successful implementation of the project. Afterwards, patient data and samples can be made available to other groups within the network for work on numerous issues.