title: The DYT1 gene on 9q34 is responsible for most cases of early limb-onset idiopathic torsion dystonia in non-Jews.
abstract: Idiopathic torsion dystonia (ITD) is characterized by involuntary twisting movements and postures. A gene for this disorder, DYT1, was mapped to chromosome 9q34 in 12 Ashkenazi Jewish (AJ) families and one large non-Jewish kindred. In the AJ population, strong linkage disequilibrium exists between DYT1 and adjacent markers within a 2-cM region. The associated haplotype occurs in > 90% of early limb-onset AJ cases. We examined seven non-Jewish ITD families of northern European and French Canadian descent to determine the extent to which early-onset ITD in non-Jews maps to DYT1. Results are consistent with linkage to the DYT1 region. Affected individuals in these families are clinically similar to the AJ cases; i.e., the site of onset is predominantly in the limbs and at least one individual in each pedigree had onset before age 12 years. None carries the AJ haplotype; therefore, they probably represent different mutations in the DYT1 gene. The two French Canadian families, however, display the same haplotype. Estimates of penetrance in non-Jewish families range from .40 to .75. We identified disease gene carriers and, with adjustments for age at onset, obtained a direct estimate of penetrance of .46. This is consistent with estimates of 30%-40% in the AJ population. Two other non-Jewish families with atypical ITD (later onset and/or cranial or cervical involvement) are not linked to DYT1, which indicates involvement of other genes in dystonia.
authors.affiliation: Department of Neurology, Oregon Health Sciences University, Portland 97201.
authors.forename: P L
authors.initials: PL
authors.lastname: Kramer
authors.forename: G A
authors.initials: GA
authors.lastname: Heiman
authors.forename: T
authors.initials: T
authors.lastname: Gasser
authors.forename: L J
authors.initials: LJ
authors.lastname: Ozelius
authors.forename: D
authors.initials: D
authors.lastname: de Leon
authors.forename: M F
authors.initials: MF
authors.lastname: Brin
authors.forename: R E
authors.initials: RE
authors.lastname: Burke
authors.forename: J
authors.initials: J
authors.lastname: Hewett
authors.forename: A L
authors.initials: AL
authors.lastname: Hunt
authors.forename: C
authors.initials: C
authors.lastname: Moskowitz
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002170:Canada / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D002899:Chromosomes, Human, Pair 9; D004422:Dystonia Musculorum Deformans / Q000208:ethnology* / Q000235:genetics* / Q000473:pathology; D005060:Europe / Q000208:ethnology; D005260:Female; D005602:France / Q000208:ethnology; D015870:Gene Expression; D005799:Genes, Dominant; D008040:Genetic Linkage; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D007585:Jews / Q000235:genetics; D015993:Life Tables; D008126:Lod Score; D008297:Male; D017720:Molecular Epidemiology; D010375:Pedigree; D011110:Polymorphism, Genetic; D014481:United States / Q000453:epidemiology