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目的:分析国人多巴敏感性肌张力障碍(DRD)患者发病与三磷酸鸟苷环化水解酶Ⅰ(GCH-I)基因突变的关系。方法:来自3个家庭的5例临床确诊的DRD患者及其亲属共12名成员,经静脉采血2 ml,常规提取基因组DNA,以PCR扩增GCH-I基因,反应产物用自动DNA测序仪直接测序。结果:在A家系,先证者母亲为正常个体,基因测序显示无基因突变,其中3例患病个体DNA测序发现第2个外显子142号碱基由鸟嘌呤转换为腺嘌呤(G→A),导致半胱氨酸被替换为酪氨酸;估计其突变基因来自已故父系一方。在B家系,先证者第1个外显子71号碱基由胸腺嘧啶转换为胞嘧啶(T→C),导致亮氨酸被替换为脯氨酸;而其父母及弟均为正常个体。丙家庭无GCH-I基因突变。结论:GCH-1基因突变只是部分DRD患者的发病原因。
OBJECTIVE: To analyze the relationship between the pathogenesis of guanosine triphosphate guanosine cyclic hydrolase Ⅰ (GCH-I) gene mutation in Chinese patients with dopa-sensitive dystonia (DRD). METHODS: Five patients with clinically diagnosed DRD and their relatives from three families were enrolled in this study. Twelve patients were enrolled in the study. Genomic DNA was extracted routinely from the venous blood and GCH-I gene was amplified by PCR. The reaction product was analyzed by automatic DNA sequencer Sequencing. Results: In the A pedigree, the proband’s mother was a normal individual, and gene sequencing showed no gene mutation. DNA sequencing of 3 affected individuals revealed that the exon 142 of the exon 2 was converted from guanine to adenine (G → A), resulting in cysteine being replaced by tyrosine; it is estimated that the mutant gene is from a deceased parent. In the B pedigree, the first exon 71 of the proband was converted from thymine to cytosine (T → C), resulting in the replacement of leucine with proline; both parents and younger were normal individuals . C family without GCH-I gene mutation. Conclusion: GCH-1 gene mutation is only the cause of some DRD patients.