A COMMON POINT MUTATION IN THE TYROSINE-HYDROXYLASE GENE IN AUTOSOMALRECESSIVE L-DOPA-RESPONSIVE DYSTONIA IN THE DUTCH POPULATION

This report concerns one new mutation in the tyrosine hydroxylase (TH) gene in three patients originating from three unrelated Dutch familie s with autosomal recessive L-DOPA-responsive dystonia (DRD). In this s tudy, all exons of the TH gene were amplified by the polymerase chain reaction and subjected to analyses by single-strand conformation polym orphism. An aberrant migration pattern was observed for exon 6 of the TH gene in all patients. Direct sequencing of the coding region of exo n 6 revealed the presence of one novel missense mutation. An a698g tra nsition resulted in the substitution of the evolutionary conserved arg inine 233 by a histidine (R233H), All patients were homozygous for the mutation. This new mutation in the TH gene was confirmed by restricti on enzyme analysis with the restriction enzyme HhaI. Thus, a high prop ortion of defective TH alleles may be R233H in The Netherlands.