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Title: A new clinical and molecular form of Unverricht-Lundborg disease localized by homozygosity mapping.
Austin Authors: Berkovic, Samuel F ;Mazarib, Aziz;Walid, Simri;Neufeld, Miriam Y;Manelis, Judith;Nevo, Yoram;Korczyn, Amos D;Yin, Jinggang;Xiong, Lan;Pandolfo, Massimo;Mulley, John C;Wallace, Robyn H
Affiliation: Epilepsy Research Centre and Department of Medicine (Neurology), University of Melbourne, Austin Health, Heidelberg West, Victoria, Australia
Issue Date: 5-Jan-2005
Publication information: Brain : A Journal of Neurology 2005; 128(Pt 3): 652-8
Abstract: 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.
Gov't Doc #: 15634728
DOI: 10.1093/brain/awh377
Type: Journal Article
Subjects: Adolescent
Chromosome Mapping.methods
Chromosomes, Human, Pair 12.genetics
Disease Progression
Lod Score
Magnetic Resonance Imaging
Unverricht-Lundborg Syndrome.genetics.pathology.physiopathology
Appears in Collections:Journal articles

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