The genetics of idiopathic torsion dystonia

The controversy regarding the mode of inheritance of idiopathic torsion dystonia in the Ashkenazi Jewish population has been resolved. At one time it was believed to be inherited as an autosomal recessive disorder. But recent studies, including a prospective, systematic, blinded analysis of the first- and second-degree relatives of 43 probands with age at onset less than 28 years found the disorder to be inherited in an autosomal dominant manner with a penetrance of approximately 0.30. Linkage analysis of Ashkenazi Jewish families with multiple affected members revealed that the gene for dystonia in this population is located in the q34 region of chromosome 9. This is the same region found to encode the dominant DYT1 gene for dystonia in a large non-Jewish family with a penetrance of about 0.70. It is likely that the disorder in these two ethnic populations may be caused by the same locus, and that the difference in penetrance may reflect different mutations operating in these two populations. We have found no evidence for genetic heterogeneity in the Ashkenazi Jewish families studied for linkage analysis, but there is at least one non-Jewish family with idiopathic torsion dystonia that is not linked to this region. Allelic association in 9q34 in the Ashkenazi Jewish population has narrowed the dystonia gene to a region of less than 2 cM.