Abstracts

Progressive myoclonus epilepsy (PME) has a number of causes, of which Unverricht-Lundborg disease (ULD) is the most common. ULD is due to mutations in the cystatin B gene on chromosome 21. We identified an inbred Arab family with a clinical pattern compatible with ULD, but mutations in the cystatin B gene were absent. We sought to characterize the clinical and molecular features of the disorder. The family was studied by multiple field trips to their town to clarify details of the complex consanguineous relationships and to personally examine the family. DNA was collected for subsequent molecular analyses from 21 individuals. A genome wide screen was performed using 811 micro-satellite markers. Homozygosity mapping was used to identify loci of interest. There were 8 affected individuals. Clinical onset was at 7.3 [plusmn] 1.5 yr with myoclonic or tonic-clonic seizures. All had myoclonus that progressed in severity over time and seven had tonic-clonic seizures. Ataxia, in addition to myoclonus, occurred in all. Detailed cognitive assessment was not possible, but there was no significant progressive dementia. There was intra-family variation in severity; three required wheelchairs in adult life, the others could walk unaided. MRI, muscle and skin biopsies on one individual were unremarkable. We mapped the family to a 15 megabase region at the peri-centromeric region of chromosome 12 with a maximum lod score of 6.32. Clinically, the phenotype of individual subjects was typical of ULD, but the mean age of onset (7.3 yr versus 11 years for ULD) was younger. The locus on chromosome 12 does not contain genes for any other form of PME, nor does it have genes known to be related to cystatin B. This represents a new clinical and molecular form of PME that we have designated ULD type 2. (Supported by AES, NHMRC, Bionomics Ltd.)