Four novel mutations in the GCH1 gene of Chinese patients with dopa-responsive dystonia

Mutation detection in the guanosine triphosphate cyclohydrolase I gene (GCH1) was performed from 4 female patients with dopa-responsive dystonia (DRD). DNA sequencing revealed the presence of four novel mutations including c.2T>C(M1T), c.239G>A(S80N), c.245T>C(L82P), and IVS5+3 del AAGT. These four mutations were not found in 100 genetically unrelated healthy controls with the same ethnic background band. In all 3 childhood-onset patients, DRD started in the legs, and missense mutations were located in the coding region of GCH1. Deletion mutation in the fifth exon–intron boundary of GCH1 was detected in the adult-onset patient. Although the data presented here do not provide sufficient evidence to establish a genotype–phenotype correlation of DRD, it is important to know the clinic features and genetic defects of DRD patients, which will help prenatal diagnosis, early diagnosis, evaluate the prognosis, and facilitate causal therapy with levodopa. © 2010 Movement Disorder Society