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. 1994 Sep;55(3):468–475.

The DYT1 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
PMCID: PMC1918396  PMID: 8079990

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.

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Selected References

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  1. Anderson M. A., Gusella J. F. Use of cyclosporin A in establishing Epstein-Barr virus-transformed human lymphoblastoid cell lines. In Vitro. 1984 Nov;20(11):856–858. doi: 10.1007/BF02619631. [DOI] [PubMed] [Google Scholar]
  2. Breakefield X. O., Bressman S. B., Kramer P. L., Ozelius L., Moskowitz C., Tanzi R., Brin M. F., Hobbs W., Kaufman D., Tobin A. Linkage analysis in a family with dominantly inherited torsion dystonia: exclusion of the pro-opiomelanocortin and glutamic acid decarboxylase genes and other chromosomal regions using DNA polymorphisms. J Neurogenet. 1986 May;3(3):159–175. doi: 10.3109/01677068609106846. [DOI] [PubMed] [Google Scholar]
  3. Bressman S. B., Heiman G. A., Nygaard T. G., Ozelius L. J., Hunt A. L., Brin M. F., Gordon M. F., Moskowitz C. B., de Leon D., Burke R. E. A study of idiopathic torsion dystonia in a non-Jewish family: evidence for genetic heterogeneity. Neurology. 1994 Feb;44(2):283–287. doi: 10.1212/wnl.44.2.283. [DOI] [PubMed] [Google Scholar]
  4. Bressman S. B., de Leon D., Brin M. F., Risch N., Burke R. E., Greene P. E., Shale H., Fahn S. Idiopathic dystonia among Ashkenazi Jews: evidence for autosomal dominant inheritance. Ann Neurol. 1989 Nov;26(5):612–620. doi: 10.1002/ana.410260505. [DOI] [PubMed] [Google Scholar]
  5. Burke R. E., Fahn S., Marsden C. D., Bressman S. B., Moskowitz C., Friedman J. Validity and reliability of a rating scale for the primary torsion dystonias. Neurology. 1985 Jan;35(1):73–77. doi: 10.1212/wnl.35.1.73. [DOI] [PubMed] [Google Scholar]
  6. Cottingham R. W., Jr, Idury R. M., Schäffer A. A. Faster sequential genetic linkage computations. Am J Hum Genet. 1993 Jul;53(1):252–263. [PMC free article] [PubMed] [Google Scholar]
  7. Fahn S. The varied clinical expressions of dystonia. Neurol Clin. 1984 Aug;2(3):541–554. [PubMed] [Google Scholar]
  8. Fletcher N. A., Harding A. E., Marsden C. D. A genetic study of idiopathic torsion dystonia in the United Kingdom. Brain. 1990 Apr;113(Pt 2):379–395. doi: 10.1093/brain/113.2.379. [DOI] [PubMed] [Google Scholar]
  9. Henske E. P., Ozelius L., Gusella J. F., Haines J. L., Kwiatkowski D. J. A high-resolution linkage map of human 9q34.1. Genomics. 1993 Sep;17(3):587–591. doi: 10.1006/geno.1993.1376. [DOI] [PubMed] [Google Scholar]
  10. Kramer P. L., de Leon D., Ozelius L., Risch N., Bressman S. B., Brin M. F., Schuback D. E., Burke R. E., Kwiatkowski D. J., Shale H. Dystonia gene in Ashkenazi Jewish population is located on chromosome 9q32-34. Ann Neurol. 1990 Feb;27(2):114–120. doi: 10.1002/ana.410270203. [DOI] [PubMed] [Google Scholar]
  11. Kwiatkowski D. J., Henske E. P., Weimer K., Ozelius L., Gusella J. F., Haines J. Construction of a GT polymorphism map of human 9q. Genomics. 1992 Feb;12(2):229–240. doi: 10.1016/0888-7543(92)90370-8. [DOI] [PubMed] [Google Scholar]
  12. Kwiatkowski D. J., Ozelius L., Kramer P. L., Perman S., Schuback D. E., Gusella J. F., Fahn S., Breakefield X. O. Torsion dystonia genes in two populations confined to a small region on chromosome 9q32-34. Am J Hum Genet. 1991 Aug;49(2):366–371. [PMC free article] [PubMed] [Google Scholar]
  13. Marsden C. D., Harrison M. J. Idiopathic torsion dystonia (dystonia musculorum deformans). A review of forty-two patients. Brain. 1974 Dec;97(4):793–810. doi: 10.1093/brain/97.1.793. [DOI] [PubMed] [Google Scholar]
  14. Nygaard T. G., Wilhelmsen K. C., Risch N. J., Brown D. L., Trugman J. M., Gilliam T. C., Fahn S., Weeks D. E. Linkage mapping of dopa-responsive dystonia (DRD) to chromosome 14q. Nat Genet. 1993 Dec;5(4):386–391. doi: 10.1038/ng1293-386. [DOI] [PubMed] [Google Scholar]
  15. Ozelius L. J., Kramer P. L., de Leon D., Risch N., Bressman S. B., Schuback D. E., Brin M. F., Kwiatkowski D. J., Burke R. E., Gusella J. F. Strong allelic association between the torsion dystonia gene (DYT1) andloci on chromosome 9q34 in Ashkenazi Jews. Am J Hum Genet. 1992 Mar;50(3):619–628. [PMC free article] [PubMed] [Google Scholar]
  16. Ozelius L. J., Kwiatkowski D. J., Schuback D. E., Breakefield X. O., Wexler N. S., Gusella J. F., Haines J. L. A genetic linkage map of human chromosome 9q. Genomics. 1992 Nov;14(3):715–720. doi: 10.1016/s0888-7543(05)80173-9. [DOI] [PubMed] [Google Scholar]
  17. Ozelius L., Kramer P. L., Moskowitz C. B., Kwiatkowski D. J., Brin M. F., Bressman S. B., Schuback D. E., Falk C. T., Risch N., de Leon D. Human gene for torsion dystonia located on chromosome 9q32-q34. Neuron. 1989 May;2(5):1427–1434. doi: 10.1016/0896-6273(89)90188-8. [DOI] [PubMed] [Google Scholar]
  18. Pauls D. L., Korczyn A. D. Complex segregation analysis of dystonia pedigrees suggests autosomal dominant inheritance. Neurology. 1990 Jul;40(7):1107–1110. doi: 10.1212/wnl.40.7.1107. [DOI] [PubMed] [Google Scholar]
  19. Risch N. J., Bressman S. B., deLeon D., Brin M. F., Burke R. E., Greene P. E., Shale H., Claus E. B., Cupples L. A., Fahn S. Segregation analysis of idiopathic torsion dystonia in Ashkenazi Jews suggests autosomal dominant inheritance. Am J Hum Genet. 1990 Mar;46(3):533–538. [PMC free article] [PubMed] [Google Scholar]
  20. Waddy H. M., Fletcher N. A., Harding A. E., Marsden C. D. A genetic study of idiopathic focal dystonias. Ann Neurol. 1991 Mar;29(3):320–324. doi: 10.1002/ana.410290315. [DOI] [PubMed] [Google Scholar]
  21. Warner T. T., Fletcher N. A., Davis M. B., Ahmad F., Conway D., Feve A., Rondot P., Marsden C. D., Harding A. E. Linkage analysis in British and French families with idiopathic torsion dystonia. Brain. 1993 Jun;116(Pt 3):739–744. doi: 10.1093/brain/116.3.739. [DOI] [PubMed] [Google Scholar]

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