title: Four novel mutations in the GCH1 gene of Chinese patients with dopa-responsive dystonia.
abstract: 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.
authors.affiliation: Department of Neurology and Institute of Neurology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Cao
authors.forename: Lan
authors.initials: L
authors.lastname: Zheng
authors.forename: Wei-Guo
authors.initials: WG
authors.lastname: Tang
authors.forename: Qin
authors.initials: Q
authors.lastname: Xiao
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Hui-Dong
authors.initials: HD
authors.lastname: Tang
authors.forename: Song-Bin
authors.initials: SB
authors.lastname: He
authors.forename: Xi-Jin
authors.initials: XJ
authors.lastname: Wang
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: Ding
authors.forename: Sheng-Di
authors.initials: SD
authors.lastname: Chen
mesh_terms: D000328:Adult; D044466:Asian People / Q000208:ethnology / Q000235:genetics; D015259:Dopamine Agents / Q000627:therapeutic use*; D004421:Dystonia / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D006136:GTP Cyclohydrolase / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use*; D009154:Mutation / Q000235:genetics*; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA / Q000379:methods; D055815:Young Adult
chemical_list: D015259:Dopamine Agents; D007980:Levodopa; D006136:GTP Cyclohydrolase