Lehesjoki A E, Koskiniemi M
Department of Medical Genetics, Haartman Institute, University of Helsinki, Finland.
Ann Med. 1998 Oct;30(5):474-80. doi: 10.3109/07853899809002489.
Progressive myoclonus epilepsy of the Unverricht-Lundborg type is the most common cause of progressive myoclonus epilepsy worldwide. Typical features include onset at the age of 6-15 years, stimulus-sensitive myoclonus, tonic-clonic seizures, a progressive course and characteristic electroencephalographic findings with an exceptionally high sensitivity to photic stimulation. With modern anticonvulsive therapy the symptoms are relatively well controlled, and the disease may not always progress. Previously, no biochemical or pathological marker existed for the diagnosis of Unverricht-Lundborg disease. The positional cloning strategy was applied to identify the genetic defects that are responsible for this disease. The underlying gene encodes cystatin B, a cysteine protease inhibitor. The major mutation worldwide is an unstable expansion of a dodecamer minisatellite repeat unit in the promoter region of the cystatin B gene. In addition, five 'minor' mutations have been described. In the majority of patients, a reduced level of the cystatin B gene product seems to be the primary mechanism in the pathology, but the pathogenetic mechanisms are yet unknown. The molecular genetic findings have made a specific diagnosis possible and are the basis for understanding the molecular pathogenesis of the disease. This understanding may lead to the development of specific therapies for Unverricht-Lundborg disease.
翁韦里希特-伦德伯格型进行性肌阵挛癫痫是全球进行性肌阵挛癫痫最常见的病因。典型特征包括6至15岁起病、刺激敏感性肌阵挛、强直阵挛发作、病情进展以及特征性脑电图表现，对光刺激异常敏感。采用现代抗惊厥疗法，症状可得到较好控制，疾病不一定总会进展。以前，不存在用于诊断翁韦里希特-伦德伯格病的生化或病理标志物。采用定位克隆策略来鉴定导致该病的基因缺陷。相关基因编码胱抑素B，一种半胱氨酸蛋白酶抑制剂。全球主要的突变是胱抑素B基因启动子区域十二聚体微卫星重复单元的不稳定扩增。此外，还描述了5种“次要”突变。在大多数患者中，胱抑素B基因产物水平降低似乎是病理过程中的主要机制，但发病机制尚不清楚。分子遗传学研究结果使特异性诊断成为可能，并且是理解该病分子发病机制的基础。这种理解可能会促使开发针对翁韦里希特-伦德伯格病的特异性疗法。
