The objectives of the program are:
1. To organise a multicenter program of genotyping in HCM.
2. To further examine the relation between genotype and phenotype in HCM.
3. To perform in vitro and in vivo investigation of the functional consequences of mutations in the HCM disease-genes.
4. To assess the role of genotyping in risk stratification for sudden death
This Reinforced Concertation will bring together and co-ordinate European research into the molecular genetic basis and clinical expression of familial hypertrophic cardiomyopathy, an autosomal dominant heart muscle disorder which is caused by mutations in sarcomeric contractile protein genes. The program of combined clinical and molecular genetics will:
* organise a shared multicenter program of genotyping in HCM with specific laboratories responsible for particular genes
* obtain a sizeable population of clinically well characterised and genotyped HCM patients in order to examine the genotype/phenotype relation. Aspects of the phenotype to be examined include: cardiac morphology and histology and determinants of prognosis/sudden death. The influence of modifier genes on the extent and severity of left ventricular hypertrophy will be examined.
* assess the functional consequences of mutations in HCM disease genes through the development of transgenic animals
* assess the potential impact of a genetic diagnosis on the identification and management of patients at high risk of sudden death
It is anticipated that achievement of these objectives will:
* facilitate diagnosis and management of patients with HCM who are at particular risk of sudden cardiac death
* provide scientific insight into the determinants and functional development of myocardial disarray and hypertrophy in HCM and the hypertrophic process in general
* lead to European wide availability of DNA diagnosis in HCM
* provide a resource to distribute clinical and molecular know-how to other European research and clinical groups
hypertrophic cardiomyopathy, left ventricular hypertrophy, clinical and molecular genetics, sudden death, contractile proteins, genotype/phenotype relation, DNA diagnosis