A novel locus for autosomal recessive primary torsion dystonia (DYT17) maps to 20p11.22-q13.12

作者：Chouery E; Kfoury J; Delague V; Jalkh N; Bejjani P; Serre J L; Megarbane A^*

来源：Neurogenetics, 2008, 9(4): 287-293.

DOI：10.1007/s10048-008-0142-4

• dystonia
• homozygosity mapping
• lod score
• dopamine
• GABA

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.

• 出版日期2008-10