Brain Advance Access published online on January 5, 2005
Brain, doi:10.1093/brain/awh377
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Epilepsy Research Centre and Department of Medicine (Neurology), University of Melbourne, Austin Health, Victoria, Australia
* To whom correspondence should be addressed. Summary Progressive myoclonus epilepsy (PME) has a number of causes, of which Unverricht-Lundborg disease (ULD) is the most common. ULD has previously been mapped to a locus on chromosome 21 (EPM1). Subsequently, mutations in the cystatin B gene have been found in most cases. In the present work 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 microsatellite markers. Homozygosity mapping was used to identify loci of interest. There were eight affected individuals. Clinical onset was at 7.3 ± 1.5 years 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 intrafamily 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 pericentromeric region of chromosome 12 with a maximum lod score of 6.32. Although the phenotype of individual subjects was typical of ULD, the mean age of onset (7.3 years 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 form of PME and we have designated the locus as EPM1B.
Received September 30, 2004
Revised November 20, 2004
Accepted November 22, 2004
Article
A new clinical and molecular form of Unverricht-Lundborg disease localized by homozygosity mapping
2 Department of Neurology, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
3 Department of Neurology, Western Galilee Hospital, Nahariya, Israel
4 Pediatric Neuromuscular Service, Dana Children's Hospital, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
5 Department of Neurology, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Sieratzki Chair of Neurology, Tel Aviv University, Ramat Aviv, Israel
6 Center for Genomics and Bioinformatics and Department of Anatomy and Neurobiology, University of Tennessee, Memphis, TN, USA
7 Centre Hospitalier de l'Université de Montréal, Montréal, Canada
8 Centre Hospitalier de l'Université de Montréal, Montréal, Canada; Université Libre de Bruxelles, Hôpital Erasme, Brussels, Belgium
9 Department of Genetic Medicine, Women's and Children's Hospital, Adelaide, and School of Molecular and Biomedical Sciences, University of Adelaide, South Australia, Australia
10 Center for Genomics and Bioinformatics and Department of Anatomy and Neurobiology, University of Tennessee, Memphis, TN, USA; Department of Genetic Medicine, Women's and Children's Hospital, Adelaide, and School of Molecular and Biomedical Sciences, University of Adelaide, South Australia, Australia
Samuel F. Berkovic, E-mail: s.berkovic{at}unimelb.edu.au
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?