Illarioshkin S N, Markova E D, Slominsky P A, Miklina N I, Popova S N, Limborska S A, Tsuji S, Ivanova-Smolenskaya I A
Department of Neurogenetics, Institute of Neurology, Russian Academy of Medical Sciences, Moscow.
Arch Neurol. 1998 Jun;55(6):789-92. doi: 10.1001/archneur.55.6.789.
To search for mutations in the GTP cyclohydrolase I (GCH-I) gene in a set of Russian families with dopa-responsive dystonia (DRD).
Six large families with 54 affected family members and 2 patients with sporadic DRD were examined. 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 GCH-I gene was sequenced.
Three new heterozygote point mutations located within exons 1, 2, and 4 of the GCH-I gene were identified in 3 families with autosomal-dominant inheritance. All these mutations are predicted to cause amino acid changes in the highly conserved regions of the gene. In patients from 3 other families and in both patients with sporadic DRD, no alterations in the translated portion of the GCH-I gene were observed.
Mutations in the coding region of the GCH-I gene account for a significant fraction (up to half) of the patients with a typical clinical picture of DRD. None of the mutations in the GCH-I gene described so far were detected more than once, which precludes the possibility of creating simple DNA testing procedures for routine clinical practice.
在一组患有多巴反应性肌张力障碍（DRD）的俄罗斯家族中寻找鸟苷三磷酸环化水解酶I（GCH-I）基因的突变。
对六个大家族（共54名患病家族成员）以及两名散发型DRD患者进行检查。采用单链构象多态性分析进行突变筛查，随后对推测发生突变的外显子进行直接测序；对于单链构象多态性分析结果显示为正常模式的患者，对GCH-I基因的整个编码区进行测序。
在三个具有常染色体显性遗传的家族中，鉴定出位于GCH-I基因第1、2和4外显子内的三个新的杂合子点突变。所有这些突变预计会导致该基因高度保守区域的氨基酸变化。在其他三个家族的患者以及两名散发型DRD患者中，未观察到GCH-I基因翻译部分的改变。
GCH-I基因编码区的突变在具有典型DRD临床表现的患者中占相当比例（高达一半）。迄今为止所描述的GCH-I基因的突变均未被多次检测到，这排除了为常规临床实践创建简单DNA检测程序的可能性。
