Background Dopa-responsive dystonia (DRD) is a clinical syndrome characterized by early onset dystonia and a dramatic response to relatively low doses of levodopa. The autosomal dominant DRD is caused by mutations in the gene coding GTP cyclohydrolase 1 (GCH1), the enzyme that catalyzes the first step in the biosynthesis of tetrahydrobiopterin. We herein report a novel gene mutation causally links to DRD. Subject and Methods A 23-year-old woman, presented with a history of gait abnormality and leg dystonia at age 15. Her symptoms were worsened especially in recent 2 years prior to visiting neurological clinic. In view of typical diurnal variation of dystonia, a therapeutic trial with levodopa was given and there was a dramatic response. Hence, a diagnosis of DRD was tentatively made. In addition, her father has leg dystonia since his 14 years old with leg tremor. Her 2 uncles and probably her 2 grandaunts also have limbs tremor. Genetic analysis by using PCR-direct sequencing revealed a novel point mutation (c.263G>T: p. Arg88Leu) in GCH1, including her father and asymptomatic eldest sister. Conclusion We here report a Taiwanese family afflicted with DRD due to a novel missense mutation of the GCH1. The clinical features are considerably variable within the family. The findings extend the genotypic and clinical spectrum of DRD.
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