A novel de novo point mutation in the GTP cyclohydrolase I gene in a Japanese patient with hereditary progressive and dopa responsive dystonia

Hereditary progressive dystonia is characterised by lower limb dystonia of childhood onset with marked diurnal fluctuation and shows a dramatic and stable response to low dose levodopa. The disease is transmitted in autosomal dominant inheritance, and Segawa et al 1 proposed hereditary progressive dystonia as a new disease entity in the early 1970s. Dopa responsive dystonia, which was first proposed by Nygaard et al 2 in 1988, is essentially identical to hereditary progressive dystonia although it may include some other heterogeneous dystonias. The GTP cyclohydrolase I (GTP-CH I) gene on chromosome 14 is the causative gene of hereditary progressive/dopa responsive dystonia3 and more than 20 different mutations have been reported. We report a novel non-sense mutation in the GTP-CH I gene in a genetically confirmed sporadic Japanese patient. (A) Pedigree of a Japanese hereditary progressive/dopa responsive dystonia family with mutation in the GTP-CH I gene. The affected propositus is represented by solid symbol, and unaffected family members, by open symbols. (B) Agarose gel electrophoresis of Eco57I restriction pattern in the exon 1 of GTP-CH I gene. PCR product (502 …