Bandmann O, Valente E M, Holmans P, Surtees R A, Walters J H, Wevers R A, Marsden C D, Wood N W
Institute of Neurology, London, UK.
Ann Neurol. 1998 Oct;44(4):649-56. doi: 10.1002/ana.410440411.
We have studied the GTP-cyclohydrolase 1 (GCH-1) gene in 30 patients with the diagnosis of clinically definite (n = 20) or possible (n = 10) dopa-responsive dystonia (DRD) as well as in a child with atypical phenylketonuria due to complete GCH-1 deficiency. A large number of new heterozygote mutations (seven point mutations, two splice site mutations, and one deletion) as well as a new homozygote mutation in the child with atypical phenylketonuria were detected. In addition, two previously described mutations were found in two other cases. We further extended our investigation of GCH-1 to the 5' and 3' regulatory regions and report the first detection of point mutations in the 5' untranslated region. Demethylation of CpG islands does not appear to be an important causative factor for the GCH-1 mutations in DRD. In addition, we have extended the clinical phenotype of genetically proven DRD to focal dystonia, dystonia with relapsing and remitting course, and DRD with onset in the first week of life. None of our DRD patients without a mutation in GCH-1 had the 3-bp deletion recently detected in DYT1, the causative gene for idiopathic torsion dystonia with linkage to 9q34.
我们研究了30例临床确诊（n = 20）或可能（n = 10）的多巴反应性肌张力障碍（DRD）患者以及1例因完全GCH - 1缺乏导致的非典型苯丙酮尿症患儿的GTP - 环化水解酶1（GCH - 1）基因。检测到大量新的杂合子突变（7个点突变、2个剪接位点突变和1个缺失）以及非典型苯丙酮尿症患儿中的1个新的纯合子突变。此外，在另外2例中发现了2个先前描述的突变。我们进一步将对GCH - 1的研究扩展到5'和3'调控区域，并报告了在5'非翻译区域首次检测到点突变。CpG岛的去甲基化似乎不是DRD中GCH - 1突变的重要致病因素。此外，我们已将基因证实的DRD的临床表型扩展到局灶性肌张力障碍、病程复发缓解型肌张力障碍以及出生后第一周发病的DRD。我们的GCH - 1无突变的DRD患者均未检测到最近在DYT1中发现的3 bp缺失，DYT1是与9q34连锁的特发性扭转性肌张力障碍的致病基因。
