THE D216H VARIANT IN THE DYT1 GENE: A SUSCEPTIBILITY FACTOR FOR DYSTONIA IN FAMILIAL CASES?

Abstract

Primary focal dystonia is a clinically and genetically heterogeneous disorder. In contrast, early-onset generalized torsion dystonia is often caused by a heterozygous deletion of three nucleotides (GAG) in the DYT1 gene leading to the loss of a glutamic acid residue (deltaE) of the gene product TorsinA.1 Interestingly, the only nonsynonymous coding sequence variation in DYT1 , rs1801968 (D216H), was demonstrated to reduce penetrance of the GAG deletion when present in trans to this mutation.2 While one study suggested a protective effect of H216 in a small number of tested Indian patients with primary dystonia, other reports failed to show any association.3–5 The aim of the present study was to evaluate the role of D216H in German patients with familial primary dystonia and, in case of association, to establish the frequency of this variant in patients with dystonia regardless of their family history. ### Subjects. Study subjects were recruited from four movement disorders centers in Northern Germany. After obtaining informed consent and approval of the study by the local ethical standards committee, all participants underwent a standardized neurologic examination by a movement disorders specialist, and blood samples were drawn. We included 111 unrelated familial cases with primary focal or segmental dystonia, along with 241 unrelated control subjects. Family history was regarded as positive when at least one …