PME OF UNVERRICHT-LUNDBORG TYPE IN THE MEDITERRANEAN REGION - LINKAGEAND LINKAGE DISEQUILIBRIUM CONFIRM THE ASSIGNMENT TO THE EPM1 LOCUS

Seven phenotypically homogeneous Mediterranean myoclonus families were studied using DNA markers from the genetically defined EPM1 region on chromosome 21. No recombinations between the disease phenotype and th e markers studied were detected. Within the EPM1 region, the highest l ed score value of 5.07 (at Theta=0.00) was reached at locus PFKL. Sign ificant allelic association (P=0.02) between the disease mutation and PFKL was detected suggesting a founder effect in Mediterranean myoclon us. However, haplotype data using four marker loci residing within 300 kb of each other and of EPM1 suggest the occurrence of more than one m utation. The data are compatible with Mediterranean myoclonus being ca used by mutations in the EPM1 gene and strengthen the concept that a l arge subset of progressive myoclonus epilepsies conforms with Unverric ht-Lundborg disease and that this subset is an etiologically homogeneo us entity.