MICHAEL PRIZE

Dr. Thomas Sander and Dr. Gertrud Beck-Managetta, Neurologische Klinik, Campus Virchow, Humboldt-University Berlin.

Among the epileptic disorders there are many with an inherited component. It is suggested that several multiplicative genes contribute to these diseases. Identification of individual susceptibility loci is extremely difficult. First of all a highly differentiated clinical analysis and follow- up studies are essential for sorting out representative samples of index cases and their families for population studies based on linkage analyses and association studies with candidate genes. Thomas Sander and the late Gertrud Beck-Managetta worked continuously with the Berlin group on Neurogenetics and made the approach possible to refine a susceptibility locus for Juvenile Myoclonic Epilepsy designated as EJM 1, located within the HLA region on chromosome 6p. In addition, using parametric and non-parametric linkage analysis, they obtained evidence for genetic heterogeneity and possible ethnic variation.

Therefore the linkage reports support that claim, while other results suggest that EJM 1 maps centromeric to HLA- DQ within a candidate region of 15,8 cM flanked by the loci D 6S273 and D 6S426. The possible ethnic variation of the polygenic background could be permissive for different susceptibility alleles. Therefore linkage studies of complex epileptic diseases should pay attention to the ethnic descent of the families.

PD Dr. Ortrud K. Steinlein, Institut für Humangenetik, University Bonn.

While epilepsies affect at least 1% of the population worldwide, their pathogenesis remains unknown in many cases. It is, however, clear that genetic factors play a major role in the etiology of common idiopathic epilepsies, displaying a complex non-mendelian pattern of inheritance. Their molecular basis is still unknown. There exsist some rare dominantly inherited partial epilepsies, as the Nocturnal Frontal Lobe Epilepsy beginning in childhood. Here Ortrud K. Steinlein and her collaborators succeeded in mapping the underlying gene to chromosome 20 q 13.2- q 13.3, where the nicotine acetylcholine receptor alpha 4 subunit also maps which is expressed in all layers of the frontal cortex.

In all affected members of a large Australian kindred- but not in healthy controls a missense mutation was found that replaces serine with phenylalanine at codon 248 in the second transmembrane domain. Nocturnal Frontal Lobe Epilepsy is thus the first idiopathic epilepsy for which a gene has been identified.

Further analysis of this gene will unveil if it also contributes to the genetic susceptibility to the common idiopathic epilepsies.