Epilepsy is a diagnostic term for a wide variety of syndromes that are mainly characterized by recurrent seizures. Epilepsy is a common condition, affecting approximately 1% of the population, and the lifetime risk of an individual developing epilepsy is 3-5%. Epilepsy therefore falls in the category of common diseases, and has a major impact on society.
There is ample evidence for a genetic contribution to epilepsy, coming from twin studies, linkage and association studies, and from chromosomal abnormalities that display epilepsy in their associated phenotype. In particular, several genes have been detected for epilepsies that show a single gene inheritance or autosomal inheritance pattern. These genes can be identified relatively simply in large families by positional cloning. It is expected that more 'single gene' epilepsies will be unraveled as new large families are identified.
The current challenge lies in discovering the genes responsible for epilepsies showing a complex inheritance pattern, involving multiple genes and environmental factors. Idiopathic Generalized Epilepsy (IGE) is the most common form of such an epilepsy. IGE can be subdivided into several clinically distinct phenotypes such as Juvenile Myoclonic Epilepsy (JME), Juvenile Absence Epilepsy (JAE) and PhotoSensitive Epilepsy (PSE). Often, more than one phenotype occurs within a family identified through a single patient, and in some cases, more than one phenotype may occur within one patient. It is often assumed that these separate IGE sub-phenotypes are caused by a single, or limited number, of genes.
An example of independent inheritance is PSE, which is expressed by the majority of patients with JME, but has been shown to be inherited separately in an autosomal dominant fashion. PSE thus provides a prime opportunity for unraveling the complex genetic background of IGE.
We are currently performing a genome-wide linkage analysis to identify the underlying genetic factors in PSE. This work is being done with an international consortium, which gives access to a large collection of families with different origins. On a smaller scale, candidate linkage and association studies are being performed for other subtypes of IGE. Candidate genes are also screened for the presence of mutations in carefully selected subgroups of epilepsy patients. Finally, chromosomal abnormalities with epilepsy as a major phenotype are being studied for the genetic defect causing the epilepsy.
Student projects (stages)
All these areas of research provide opportunities for short-term projects.
Further Information
For further information, please contact Dr. Bobby Koeleman phone:00-31-(0)88 756 8116 or email:
B.P.C.Koeleman@umcutrecht.nl