The research group of professor Manfred Kilimann at the Department of Cell and Molecular Biology has elucidated the genetic cause of a severe heart disease in newborn children. This result will be published in the June issue of the American Journal of Human Genetics this week.
Cardiomyopathies are diseases of the heart muscle tissue and often lead to heart failure. Most of them are inborn and can be caused by gene defects (mutations) affecting various proteins needed either for the contraction or the energy supply of the heart. The subject of professor Kilimann's research was a rare but particularly malignant form of cardiomyopathy: fatal congenital nonlysosomal heart glycogenosis (FCNHG). Children with this disease have a dramatically enlarged heart (5 times the normal weight) and arrhythmia, and die from heart failure and respiratory complications at a few weeks of age.
"Earlier biochemical research had attributed this disease to a defect in an enzyme of energy metabolism, phosphorylase kinase (Phk), but when we analyzed the Phk genes, we found them to be normal. The earlier molecular explanation of FCNHG was apparently in error. We finally had the idea to look into another gene, of AMP-activated protein kinase (PRKAG2), which is also involved in energy metabolism and was known to cause a related but much milder cardiomyopathy that develops in juvenile or young adult patients. Indeed, in several patients from different countries we found exactly the same mutation. In collaboration with a British laboratory, the mutant protein was produced in the test tube, and found to be much more severely altered in its molecular properties than the mutant proteins from adult patients described previously", says Manfred Kilimann.