To determine whether reduced striatal D2 receptor binding reported in patients with idiopathic torsion dystonia is associated with the genotype, the authors used PET and [11C]-raclopride to assess non-manifesting carriers of the DYT1 mutation.
A comparison of the phenotype in the present family and other non-DYT1 families shows striking overlapping features differing from those of DYT1idiopathic torsion dystonia.
Over the last two decades an increasing number of genetic causes have been identified, including an important genetic cause for early-onset primary torsion dystonia (PTD): a GAG deletion in exon 5 of DYT1, a gene that encodes torsinA.
The DYT1 gene responsible for early-onset, idiopathic torsion dystonia (ITD) in the Ashkenazi Jewish population, as well as in one large non-Jewish family, has been mapped to chromosome 9q32-34.
We tested 24 families and six isolated cases with ITD and found 14 individuals from six French families who carried this mutation, indicating that 20% of the affected families carried the DYT1 mutation.
None of our DRD patients without a mutation in GCH-1 had the 3-bp deletion recently detected in DYT1, the causative gene for idiopathic torsion dystonia with linkage to 9q34.
Our findings highlight the sustained benefit from DBS and the importance of early referral for DBS in children with medically refractory DYT1primary torsion dystonia, which can lead to improved long-term benefits.
To develop diagnostic testing guidelines for the DYT1 GAG deletion in the Ashkenazi Jewish (AJ) and non-Jewish (NJ) primary torsion dystonia (PTD) populations and to determine the range of dystonic features in affected DYT1 deletion carriers.
Laboratory investigations failed to identify any abnormality, and linkage analysis excluded the region containing the DYT1 locus, indicating that the gene responsible for idiopathic torsion dystonia was not implicated in this family.