Molecular genetic analysis of torsion dystonia in Russia

For the first time in Russia, analysis of the GCH-1 and DYT1 genes was carr ied out for the purpose of direct DNA diagnostics in families with various forms of hereditary torsion dystonia (TD). Four new missense mutations (Met 102Lys, Thr94Lys, Cys141Trp, and Ser176Thr) in the GCH-1 gene were found in patients with dopa-responsive dystonia (DRD), testifying to a genetic hete rogeneity of this clinical form of TD. The distribution of the major del GA G mutation in exon 5 of the DYT1 gene was studied in patients with non-dopa -responsive dystonia (NDRD). In total, the mutation was found in 68% of the patients. The frequency of this mutation in Ashkenazi Jews with NDRD was 1 00% (twice higher than in Slavonic families), suggesting the founder effect reported for NDRD in this ethnic group. Mutations of the GCH-1 and DYT1 ge nes were also found in patients with atypical and questionable cases of TD, which are difficult to diagnose with methods other than DNA analysis. The data obtained made it possible to extend the spectrum of clinical signs of DRD and NDRD and to revise the views on true penetrance of the correspondin g mutant genes, which is important for medical genetic counseling in affect ed families.