A novel locus for autosomal recessive primary torsion dystonia (DYT17) maps to 20p11.22-q13.12
A novel locus for autosomal recessive primary torsion dystonia (DYT17) maps to 20p11.22-q13.12
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DOI：
10.1007/s10048-008-0142-4
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发表时间：
2008-10-01
期刊：
影响因子：
2.2
通讯作者：
Megarbane, A.
中科院分区：
文献类型：
--
作者：
Chouery, E.;Kfoury, J.;Megarbane, A.
原发性扭转性肌张力障碍是一组临床和遗传异质性的运动障碍。到目前为止，已经描述了15种不同类型的肌张力障碍，其中14个位点已经被定位，但只有7个基因被确定。已经描述了几种不同的遗传模式，包括外显率降低的常染色体显性遗传（12个基因座）、隐性X连锁遗传（1个基因座）和常染色体隐性遗传（3个基因座）。在这项研究中，我们描述了本地化的一种新形式的常染色体隐性遗传，原发性局灶性扭转肌张力障碍使用全基因组搜索在一个大型的血缘黎巴嫩家庭与三个受影响的个人。利用382个微卫星标记进行了纯合性定位。连锁分析和单倍型的建设使我们能够确定一个新的基因座指定为DYT17，在20号染色体上的20.5 Mb的间隔。在这段时间内传播的270个已知基因中，有27个候选基因被测试并排除为该疾病的负责基因。为了确定DYT17中的致病基因，需要通过鉴定与20号染色体连锁的其他肌张力障碍家族和在精细间隔中的候选基因测序进行精细定位。
Primary torsion dystonia is a clinically and genetically heterogeneous group of movement disorders. Fifteen different types of dystonia have been described to date, of whom 14 loci have been mapped, but only seven genes identified. Several different modes of inheritance have been described, including autosomal dominant transmission with reduced penetrance (12 loci), recessive X-linked (one locus), and autosomal recessive transmission (three loci). In this study, we describe the localization of a novel form of autosomal recessive, primary focal torsion dystonia using a genomewide search in a large consanguineous Lebanese family with three affected individuals. Homozygosity mapping with 382 microsatellite markers was conducted. Linkage analysis and haplotype construction allowed us to identify a novel locus designated as DYT17, within a 20.5-Mb interval on chromosome 20. Of the 270 known genes spread on this interval, 27 candidate genes were tested and excluded as responsible for the disease. Fine mapping by identification of other dystonia families linked to chromosome 20 and sequencing of candidate genes in the refined interval is required in order to identify the causative gene in DYT17.