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 ofJapanese patients, but is now increasingly recognized in other countries.Recently the GTP cyclohydrolase I (GTPCH) gene was isolated as the firstcausative gene for dopa-responsive dystonia (DRD). Mutations wereidentified in three Japanese families with autosomal dominantly inheritedDRD and in one sporadic Japanese patient. Characterisation of theexon-intron boundaries of this gene has now allowed the analysis ofmutations at the level of genomic DNA. Amplifying all six exons, weanalyzed the GTPCH gene in nine British families with 33 affected familymembers and in three sporadic cases and found six new mutations. Only pointmutations were found, causing a stop codon in one family and an amino acidchange in highly conserved regions of the gene in a further four familiesand in one sporadic case. None of these mutations were detected more thanonce and none of the mutations previously described were found in ourpatients. No mutations were identified in four families and in two sporadiccases.