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

Research output: Contribution to journalArticle

102 Citations (Scopus)

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

Fingerprint

Dystonia Musculorum Deformans
Extremities
Haplotypes
Penetrance
Age of Onset
Genes
Dystonia
Linkage Disequilibrium
Dyskinesias
Pedigree
Posture
Population
Chromosomes
Mutation

ASJC Scopus subject areas

  • Genetics

Cite this

Kramer, P. L., Heiman, G. A., Gasser, T., Ozelius, L. J., De Leon, D., Brin, M. F., ... Bressman, S. B. (1994). The DYTI Gene on 9q34 Is Responsible for Most Cases of Early Limb-Onset Idiopathic Torsion Dystonia in Non-Jews. American Journal of Human Genetics, 55(3), 468-475.

The DYTI Gene on 9q34 Is Responsible for Most Cases of Early Limb-Onset Idiopathic Torsion Dystonia in Non-Jews. / Kramer, P. L.; Heiman, G. A.; Gasser, T.; Ozelius, L. J.; De Leon, D.; Brin, M. F.; Burke, R. E.; Hewett, J.; Hunt, A. L.; Moskowitz, C.; Nygaard, T. G.; Wilhelmsen, K. C.; Fahn, S.; Breakefield, X. O.; Risch, N. J.; Bressman, S. B.

In: American Journal of Human Genetics, Vol. 55, No. 3, 1994, p. 468-475.

Research output: Contribution to journalArticle

Kramer, PL, Heiman, GA, Gasser, T, Ozelius, LJ, De Leon, D, Brin, MF, Burke, RE, Hewett, J, Hunt, AL, Moskowitz, C, Nygaard, TG, Wilhelmsen, KC, Fahn, S, Breakefield, XO, Risch, NJ & Bressman, SB 1994, 'The DYTI Gene on 9q34 Is Responsible for Most Cases of Early Limb-Onset Idiopathic Torsion Dystonia in Non-Jews', American Journal of Human Genetics, vol. 55, no. 3, pp. 468-475.
Kramer, P. L. ; Heiman, G. A. ; Gasser, T. ; Ozelius, L. J. ; De Leon, D. ; Brin, M. F. ; Burke, R. E. ; Hewett, J. ; Hunt, A. L. ; Moskowitz, C. ; Nygaard, T. G. ; Wilhelmsen, K. C. ; Fahn, S. ; Breakefield, X. O. ; Risch, N. J. ; Bressman, S. B. / The DYTI Gene on 9q34 Is Responsible for Most Cases of Early Limb-Onset Idiopathic Torsion Dystonia in Non-Jews. In: American Journal of Human Genetics. 1994 ; Vol. 55, No. 3. pp. 468-475.
@article{865cbfdd6d4f4fac8f97b8a9305789a4,
title = "The DYTI 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.",
author = "Kramer, {P. L.} and Heiman, {G. A.} and T. Gasser and Ozelius, {L. J.} and {De Leon}, D. and Brin, {M. F.} and Burke, {R. E.} and J. Hewett and Hunt, {A. L.} and C. Moskowitz and Nygaard, {T. G.} and Wilhelmsen, {K. C.} and S. Fahn and Breakefield, {X. O.} and Risch, {N. J.} and Bressman, {S. B.}",
year = "1994",
language = "English (US)",
volume = "55",
pages = "468--475",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "3",

}

TY - JOUR

T1 - The DYTI Gene on 9q34 Is Responsible for Most Cases of Early Limb-Onset Idiopathic Torsion Dystonia in Non-Jews

AU - Kramer, P. L.

AU - Heiman, G. A.

AU - Gasser, T.

AU - Ozelius, L. J.

AU - De Leon, D.

AU - Brin, M. F.

AU - Burke, R. E.

AU - Hewett, J.

AU - Hunt, A. L.

AU - Moskowitz, C.

AU - Nygaard, T. G.

AU - Wilhelmsen, K. C.

AU - Fahn, S.

AU - Breakefield, X. O.

AU - Risch, N. J.

AU - Bressman, S. B.

PY - 1994

Y1 - 1994

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0027930349&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027930349&partnerID=8YFLogxK

M3 - Article

C2 - 8079990

AN - SCOPUS:0027930349

VL - 55

SP - 468

EP - 475

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 3

ER -