一种新型错义突变使多巴反应性肌张力障碍中的GTP环化水解酶I失活。
A novel missense mutant inactivates GTP cyclohydrolase I in dopa-responsive dystonia.
作者信息
Hirano M, Komure O, Ueno S
机构信息
Department of Medical Genetics, Nara Medical University, Kashihara, Japan.
出版信息
Neurosci Lett. 1999 Feb 5;260(3):181-4. doi: 10.1016/s0304-3940(98)00984-7.
Dopa-responsive dystonia (DRD) due to mutant GTP cyclohydrolase I (GCH) shows the considerable heterogeneity of clinical phenotypic expression. To explain the clinical diversity, we studied a Japanese family with a novel mutant GCH (GCH-G90V), where an affected heterozygote had a higher mutant/normal mRNA ratio than an unaffected heterozygote. Coexpression experiments using the mutant with wild-type GCH showed that GCH-G90V inactivated the normal enzyme in a dose-dependent manner, suggesting that the dominant negative effect of a mutant GCH on the normal enzyme might be one of the molecular mechanisms for the clinical heterogeneity of DRD.
由突变型鸟苷三磷酸环化水解酶I（GCH）引起的多巴反应性肌张力障碍（DRD）表现出临床表型表达的显著异质性。为了解释临床多样性，我们研究了一个携带新型突变型GCH（GCH-G90V）的日本家族，其中患病杂合子的突变型/正常mRNA比率高于未患病杂合子。使用突变型GCH与野生型GCH进行的共表达实验表明，GCH-G90V以剂量依赖的方式使正常酶失活，这表明突变型GCH对正常酶的显性负效应可能是DRD临床异质性的分子机制之一。
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