Search for a founder mutation in idiopathic focal dystonia from northern Germany

Both the discovery of the DYT1 gene on chromosome 9q34 in autosomal dominan t early-onset torsion dystonia and the detection of linkage for one form of adult-onset focal dystonia to chromosome 18p (DYT7) in a family from north ern Germany provide the opportunity to further investigate genetic factors in the focal dystonias. Additionally, reports of linkage disequilibrium bet ween several chromosome 18 markers and focal dystonia, both in sporadic pat ients from northern Germany and in members of affected families from centra l Europe suggest the existence of a founder mutation underlying focal dysto nia in this population. To evaluate the role of these loci in focal dystoni a, we tested 85 patients from northern Germany who had primary focal dyston ia, both for the GAG deletion in the DYT1 gene on chromosome 9q34 and for l inkage disequilibrium at the chromosome 18p markers D18S1105, D18S1098, D18 S481, and D18S54. None of these patients had the GAG deletion in the DYT1 g ene. Furthermore, Hardy-Weinberg analysis of markers on 18p in our patient population and in 85 control subjects from the same region did not support linkage disequilibrium. Taken together, these results suggest that most cas es of focal dystonia in patients of northern German or central European ori gin are due neither to the GAC deletion in DYT1 nos to a proposed founder m utation on chromosome 18p but must be caused by other genetic or environmen tal factors.