title: A novel locus for autosomal recessive primary torsion dystonia (DYT17) maps to 20p11.22-q13.12.
abstract: 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.
authors.affiliation: Unité de Génétique Médicale, Faculté de Médecine, Université Saint-Joseph, Beirut, Lebanon.
authors.forename: E
authors.initials: E
authors.lastname: Chouery
authors.forename: J
authors.initials: J
authors.lastname: Kfoury
authors.forename: V
authors.initials: V
authors.lastname: Delague
authors.forename: N
authors.initials: N
authors.lastname: Jalkh
authors.forename: P
authors.initials: P
authors.lastname: Bejjani
authors.forename: J L
authors.initials: JL
authors.lastname: Serre
authors.forename: A
authors.initials: A
authors.lastname: Mégarbané
mesh_terms: D000328:Adult; D002874:Chromosome Mapping; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D003241:Consanguinity; D003598:Cytoskeletal Proteins / Q000235:genetics; D004422:Dystonia Musculorum Deformans / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D007861:Lebanon; D008126:Lod Score; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D018895:Microsatellite Repeats; D009479:Neuropeptides / Q000235:genetics; D010375:Pedigree; D017481:Receptors, Somatostatin / Q000235:genetics; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000235:genetics
chemical_list: D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D009479:Neuropeptides; D017481:Receptors, Somatostatin; C492245:SLC32A1 protein, human; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C120557:erythrocyte membrane protein band 4.1-like 1; C098681:somatostatin receptor subtype-4