The DYTI Gene on 9q34 Is Responsible for Most Cases of Early Limb-Onset Idiopathic Torsion Dystonia in Non-Jews

P. L. Kramer, G. A. Heiman, T. Gasser, L. J. Ozelius, D. De Leon, M. F. Brin, R. E. Burke, J. Hewett, A. L. Hunt, C. Moskowitz, T. G. Nygaard, K. C. Wilhelmsen, S. Fahn, X. O. Breakefield, N. J. Risch, S. B. Bressman

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114 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)468-475
Number of pages8
JournalAmerican Journal of Human Genetics
Volume55
Issue number3
StatePublished - 1994

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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