The Clinical Features Of Dopa-responsive Dystonia(DRD) And The GCH-1 Gene Mutation In A Chinese Family

Objective :To study the clinical features of hereditary dopa-responsive dystonia(DRD) and the related guanosine triphosphate cyclohydrolase 1(GCH-Ⅰ) gene mutation in a Chinese family,and provide evidence to understand the clinical characteristics and molecular biological basis for dopa-responsive dystonia in Chinese.Methods Clinical data of a family with a clinical diagnosis of dopa-responsive dystonia(DRD) from Lujiang county in Anhui Province were collected and follow-up visit was conducted for 3 years. Blood samples were collected from the family members and their genome DNA was extracted by standard technique. We used PCR technology to amplify all of 6 exons of guanosine triphosphate cyclohydrolase 1 (GCH-Ⅰ) gene, and then all the reaction products were sequenced by DNA sequencer.Results There were four affected members in this family,one male and three female,the onset age was from 7 years old to 36 years old,the disease duration was from 6 years to 37 years.The clinical features were mainly dystonia and parkinsonism, consistent with reported cases in document , but the symptoms severity showed significant difference among affected individuals,more severe symptoms with earlier onset age. Two patients were disabled for jiont contracture and limb deformity due to delayed treatment.All affected family members had quite good response to levedopa treatment, but one patient developed severe dyskinesia after long-term high-dose treatment , which was rarely reported before. DNA sequencing showed a point mutation with transition of T to A at the 102 base of exon 4 of GCH-Ⅰgene, resulting in a substitution of arginine by serine at point of 176 in the GCH-Ⅰprotein. The GCH-Ⅰgene sequences were normal in other family members with normal phenotype.Conclusion1. The symptom severity of hereditary DRD may vary significantly among individuals even in the same family, the symptoms being more serious with earlier onset age.2. Patients with DRD have good reponse to levedopa treatment and should be diagnosed and treated as early as possible , delayed treatment may lead to disability.Although seldom occured, affected individuals can developed severe dyskinesia after long-term improper high-dose levedopa therapy.3. Mutation with T→A at point 102 of exon 4 in GCH-Ⅰgene should be considered as one of the etiological basis for dopa-responsive dystonia.