Evaluation of the role of the D2 dopamine receptor in myoclonus dystonia

A novel Val(154)-->Ile mutation in the D2 dopamine receptor (DRD2) on chrom osome 11q23 has recently been shown to be associated with myoclonus dystoni a (M-D) in one large family. Sequence analysis of the DRD2 gene in 5 M-D pa tients from different families did not reveal any mutations, nor was there evidence of linkage to the 11q23 region in the DRD2 gene in four other fami lies. Receptor binding and signal transduction assays of the DRD2 mutant an d wild-type receptors revealed identical agonist and antagonist affinities and functional responses. These studies suggest that M-D is genetically het erogeneous. The molecular mechanisms through which the Val-->Ile mutation m ay contribute to M-D remain to be determined.