Abstracts

RATIONALE: The aim is to map and identify the gene(s) mutated in autosomal recessive juvenile myoclonic epilepsy (JME). METHODS: Consanguineous Saudi Arabian families in which JME appears to segregate as an autosomal recessive trait have been ascertained. Linkage analysis methods have been used to establish a genetic localisation. The strategy employed, homozygosity mapping, exploits the power, in linkage terms, of consanguineous families. In an inbred population, the disease gene, together with a small surrounding region, will be inherited from a common ancestor. For autosomal recessive conditions, affected individuals will share two copies of this common haplotype. RESULTS: In the original large pedigree, a region of haplotype sharing on chromosome 6q is currently being investigated. Linkage analysis of the region using the GENEHUNTER program gives a maximum multipoint lod score of 4.6 (assuming autosomal recessive inheritance and a penetrance of 0.9). The chromosome 6 sequencing project is being carried out at the Sanger Centre, but the sequence for this region on 6q is not yet complete. The defined region contains no known candidate genes for epilepsy, and so efforts are being applied to narrowing the region. Additional microsatellite markers identified from sequencing data are being typed in these pedigrees to further narrow the candidate region. The microsatellite marker order for this region is conflicting at present. Radiation hybrid mapping of the region is therefore being performed to establish a consensus marker order. The size of this candidate region is unknown because of conflicting mapping data. CONCLUSIONS: A disease gene locus for autosomal recessive JME has been mapped to a 3.2-10.8 cM region on chromosome 6q.