DOPA-RESPONSIVE DYSTONIA IN BRITISH PATIENTS - NEW MUTATIONS OF THE GTP-CYCLOHYDROLASE-I GENE AND EVIDENCE FOR GENETIC-HETEROGENEITY

Dopa-responsive dystonia (DRD) was originally described in a series of Japanese patients, but is now increasingly recognized in other countr ies. Recently the GTP cyclohydrolase I (GTPCH) gene was isolated as th e first causative gene for dopa-responsive dystonia (DRD). Mutations w ere identified in three Japanese families with autosomal dominantly in herited DRD and in one sporadic Japanese patient. Characterisation of the exon-intron boundaries of this gene has now allowed the analysis o f mutations at the level of genomic DNA. Amplifying all six exons, we analyzed the GTPCH gene in nine British families with 33 affected fami ly members and in three sporadic cases and found six new mutations, On ly point mutations were found, causing a stop codon in one family and an amino acid change in highly conserved regions of the gene in a furt her four families and in one sporadic case. None of these mutations we re detected more than once and none of the mutations previously descri bed were found in our patients. No mutations were identified in four f amilies and in two sporadic cases.