通过纯合子定位法确定的新的临床和分子类型的Unverricht-Lundborg病

作     者：Berkovic S.F. Mazarib A. Walid S. 郭俊 

作者机构：Epilepsy Research Centre Neurosciences Building Repatriation Campus Heidelberg West Vic. 3081 Australia Dr. 

出 版 物：《世界核心医学期刊文摘（神经病学分册）》 (Digest of the World Core Medical Journals:Clinical Neurology)

年 卷 期：2005年第1卷第8期

页      面：16-16页

学科分类：1002[医学-临床医学] 100204[医学-神经病学] 10[医学] 

主　　题：纯合子定位法 肌阵挛性癫痫 蛋白酶抑制剂 基因突变 分子学 皮肤活组织检查 进行性痴呆 基因座 着丝粒 共济失调 

摘      要：Progressive myoclonus epilepsy (PME) has a number of causes,of which Unverrich t-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 cystati n B gene were absent. We sought to characterize the clinical and molecular featu res of the disorder. The family was studied by multiple field trips to their tow n to clarify details of the complex consanguineous relationships and to personal ly examine the *** was collected for subsequent molecular analyses from 2 1 individuals. A genome-wide screen was performed using 811 microsatellite mark ers. Homozygosity mapping was used to identify loci of interest. There were eigh t affected *** onset was at 7.3 ±1.5 years with myoclonic or t onic-clonic seizures. All had myoclonus that progressed in severity over time a nd seven had tonic-clonic seizures. Ataxia, in addition to myoclonus, occurred in all. Detailed cognitive assessment was not possible, but there was no signifi cant progressive dementia. There was intrafamily variation in severity; three re quired 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 doe s it have genes known to be related to cystatin *** represents a new form of PME and we have designated the locus as EPM1B.