Genetic and clinical characterisation of arrhythmogenic cardiomyopathy

PhD ceremony: Mr. P.A. van der Zwaag, 12.45 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Genetic and clinical characterisation of arrhythmogenic cardiomyopathy

Promotor(s): prof. R.M.W. Hofstra, prof. M.P. van den Berg

Faculty: Medical Sciences

Sudden death at a young age is the most devastating outcome of cardiomyopathy (heart muscle disease). Early detection of the disease in family members is of great importance since cardiomyopathies are often genetically inherited. A mutation in the DNA is found in about half of the cardiomyopathy patients. Arrhythmogenic cardiomyopathy, one type of cardiomyopathy, is mainly characterised by severe cardiac arrhythmias, which can lead to sudden cardiac death. The aim of this project was to identify novel genes/mutations causing arrhythmogenic cardiomyopathy.

We developed a new method to identify these genes/mutations and successfully applied it to two families. These and other families showed that the same mutation can manifest itself in various ways: from sudden cardiac death at a young age to elderly individuals who remained asymptomatic. To gain more insight into this variation, all mutations in genes that can cause arrhythmogenic cardiomyopathy were recorded in an online database ( www.arvcdatabase.info ). The database has been visited over 125,000 times from more than 50 countries. The most important result of this project is the discovery of a mutation in the PLN gene. The mutation has shown to be the most frequent cause of inherited cardiomyopathy in the Netherlands and was so far found in over 100 families. It is especially prevalent in the northern parts of the Netherlands and probably originates from an ancestor in the eastern part of the province of Friesland some 600-800 years ago. An important result of this project is that more families affected by an inherited cardiomyopathy can be detected and treated at an early stage.

Read also the press release: Gene for cardiomyopathy can be traced back to joint Frisian ancestor