Schilling Section of Clinical and Molecular Neurogenetics, Department of Neurology, University of Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany.
Curr Neurol Neurosci Rep. 2010 May;10(3):199-206. doi: 10.1007/s11910-010-0107-5.
Advances in the genetics of dystonia have further elucidated the pathophysiology of this clinically and etiologically heterogeneous group of movement disorders. Currently, 20 monogenic forms of dystonia, designated by the acronym DYT, are grouped as 1) pure dystonias, 2) dystonia-plus syndromes, and 3) paroxysmal dystonias/dyskinesias. We summarize recently discovered genes and loci, including the 1) detection of two primary dystonia genes (DYT6, DYT16), 2) identification of the DYT17 locus, 3) association of a dystonia/dyskinesia phenotype with a gene previously linked to GLUT1 (glucose transporter of the blood-brain barrier) deficiency syndrome (DYT18), 4) designation of paroxysmal kinesigenic and nonkinesigenic dyskinesia as DYT19 and DYT20, and 5) redefinition of DYT14 as DYT5. Further, we review current knowledge regarding genetic modifiers and susceptibility factors. Because recognizing and diagnosing monogenic dystonias have important implications for patients and their families with regard to counseling, prognosis, and treatment, we highlight clinical "red flags" of individual subtypes and review guidelines for genetic testing.
在扭转痉挛遗传学方面的进展进一步阐明了这一具有临床和病因学异质性的运动障碍疾病群体的病理生理学。目前，20 种单基因形式的扭转痉挛，用缩写 DYT 表示，分为 1）单纯型扭转痉挛，2）扭转痉挛伴发综合征，和 3）发作性扭转痉挛/运动障碍。我们总结了最近发现的基因和基因座，包括 1）两个原发性扭转痉挛基因（DYT6，DYT16）的检测，2）DYT17 基因座的鉴定，3）与先前与葡萄糖转运体 1（血脑屏障葡萄糖转运蛋白）缺乏综合征（DYT18）相关的基因相关的扭转痉挛/运动障碍表型的关联，4）阵发性运动诱发性和非运动诱发性运动障碍分别命名为 DYT19 和 DYT20，以及 5）DYT14 重新定义为 DYT5。此外，我们回顾了关于遗传修饰因子和易感性因素的现有知识。因为识别和诊断单基因性扭转痉挛对患者及其家属的咨询、预后和治疗具有重要意义，所以我们强调了各个亚型的临床“警示标志”，并回顾了基因检测的指南。
