The mutations in GTP cyclohydrolase Ⅰ gene in Chinese patients with dopa responsive dystonia / 中华神经科杂志

ABSTRACT

Objective To detect the mutations in coding region of the guanosine triphosphate cyclohydrolase Ⅰ (GCH1) gene in Chinese patients with dopa-responsive dystonia (DRD).Methods Two families with five affected family members and six patients with sporadic DRD were examined, as well as their eighteen relatives and twenty normal members. Mutation screening was performed using single-strand conformation polymorphism analysis followed by direct sequencing of the presumably mutated exons; in patients whose results showed a normal pattern on single-strand conformation polymorphism analysis, the entire coding region of the GCH1 gene was sequenced. To confirm the mutation, a pair of primers was designed, which produced a restrictive site for SphI.Results DNA sequencing revealed a new heterozygous A224G missense mutation (Tyr75Cys) located within exon 1 in one family with autosomal-dominant inheritance. The mutation was confirmed with restriction enzyme analysis; it was not present in 20 control alleles. Restriction enzyme analysis also detects two systematic gene mutation carriers. In patients from the other family and patients with sporadic DRD, no alterations in the translated portion of the GCH1 gene were observed. Direct sequencing also showed that there existed gene polymorphisms in intron 1 and intron 3 which neared the exon2 and exon3 respectively in Chinese.Conclusions We describe a new missense mutation (Tyr75Cys) in the GCH1 gene. Mutation in the coding region of the gene might be accounted for a part of patients with DRD.