A novel mutation in the GTP cyclohydrolase I gene associated with a broad range of clinical presentations in a family with autosomal dominant dopa-responsive dystonia

We examined a large family of Ashkenazi Jewish origin with autosomal domina nt dopa-responsive dystonia (DRD). Mutation analysis of the GTP cyclohydrol ase I gene revealed in affected members a novel point mutation (a C/A chang e in exon 1) resulting in a threonine-to-lysine substitution at residue 94. The mutation was characterized by variable expressivity and was associated with either a 'classical' DRD phenotype or various atypical phenotypes, su ch as subtle transitory equinovarus postures of the feet or isolated hand t remor. This observation demonstrates the significance of the molecular test ing in establishing the clinical diagnosis of DRD. Eur J Neurol 6:605-608 ( C) 1999 Lippincott Williams & Wilkins.