GCH1 Mutation and Clinical Study of Chinese Patients with Dopa-responsive Dystonia

被引:20
作者
Liu, Xin [1 ]
Zhang, Shu-Shan [1 ]
Fang, Deng-Fu [1 ]
Ma, Ming-Yi [2 ]
Guo, Xiao-Yan [1 ]
Yang, Yuan [2 ]
Shang, Hui-Fang [1 ]
机构
[1] Sichuan Univ, Dept Neurol, W China Hosp, Chengdu 610064, Sichuan, Peoples R China
[2] Sichuan Univ, Dept Genet, W China Hosp, Chengdu 610064, Sichuan, Peoples R China
关键词
dopa-responsive dystonia; clinical feature; GCH1; gene; CYCLOHYDROLASE-I GENE; DELETION; FAMILY;
D O I
10.1002/mds.22976
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Dopa-responsive dystonia (DRD) is typically caused by heterozygous mutations in GTP cyclohydrolase 1 gene (GCH1). Our aim was to investigate the clinical and genetic features of Chinese DRD patients. We analyzed a cohort of Chinese DRD patients' clinical data. Mutation of the GCH1 gene was screened by direct sequencing. Additionally, multiplex ligation-dependent probe amplification (MLPA) assay targeting the GCH1 and the TH gene to evaluate large exon deletion or duplicate mutation of the genes were performed in point mutation-negative patients. Ten sporadic DRD patients and two pedigrees including six patients were included in the study. The onset age ranged from 3 to 15 years old. All patients initially presented with walking problems due to lower limb dystonia. The delay between onset and diagnosis ranged from 1 to 42 years old. The symptoms were completely or near-completely abolished with low close levodopa treatment (dosages ranged from 25 mg to 400 mg/day). Direct sequencing in 14 patients found two known mutations (Gly203Arg in exon 5 in four unrelated patients and Met102Lys in exon I in one patient) and one new mutation (Thr186Ile mutation in exon 5 in two unrelated pedigrees). A heterozygous exon 2 deletion in the GCH1 gene was found in one of three point mutation-negative patients by MLPA analysis. Our clinical findings in DRD patients were consistent with other studies. GCH1 gene mutations were quite common in Chinese patients. MPLA should be performed in routine deletion analysis of GCH1 in point mutation-negative DRD patients. (C) 2010 Movement Disorder Society
引用
收藏
页码:447 / 451
页数:5
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