THE DYTI GENE ON 9Q34 IS RESPONSIBLE FAR MOST CASES OF EARLY LIMB-ONSET IDIOPATHIC TORSION DYSTONIA IN NON-JEWS

Idiopathic torsion dystonia (ITD) is characterized by involuntary twis ting movements and postures. A gene for this disorder, DYT1, was mappe d to chromosome 3q34 in 12 Ashkenazi Jewish (AJ) families and one larg e non-Jewish kindred. In the AJ population, strong linkage disequilibr ium 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 limb s and at least one individual in each pedigree had onset before age 12 years. None carries the AJ haplotype; therefore, they probably repres ent different mutations in the DYT1 gene. The two French Canadian fami lies, 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 est imate of penetrance of .46. This is consistent with estimates of 30%-4 0% in the AJ population. Two other non-Jewish families with atypical I TD (later onset and/or cranial or cervical involvement) are not linked to DYT1, which indicates involvement of other genes in dystonia.