国人多巴敏感性肌张力障碍的分子遗传学研究

目的：分析国人多巴敏感性肌张力障碍（DRD）患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患及其亲属共12名成员，经静脉采血2ml，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，先证母亲为正常个休，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），导致半胱氨酸被为酪氨酸；估计其突变基因来自自己故父系一方。在B有系，先证第1个外显子 71号碱基由胸腺嘧啶为胞嘧啶（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患的发病原因。

Molecular genetics of dopa-responsive dystonia in Chinese

Objective: To investigate the relationship between the morbidity of dopa-responsive dystonia (DRD) and GTP cyclohydrolase I (GCH- I ) gene mutation in Chinese. Methods:Venous blood (2 ml) was obtained from each of the 12 members (including 5 patients and their relatives) from 3 families and their genome DNA was extracted by standard technique. GCH- I genes were amplified by PCR.the reaction products were sequenced by DNA sequencer. Results:In family A, the mother was a normal individual without GCH- I gene mutation,but in the 3 patients,a transition of G to A at the 142 base of exon 2 was found,resulting in a substitution of cysteine by tyrosine. In family B,the proband had a transition of T to C at the 71 base of exon 1 resulting in a substitution of leucine by proline; But her parents and brother were normal. There was no GCH- I gene mutation in family C. Conclusion: GCH- I gene mutation is the etiological basis of dopa-responsive dystonia in some Chinese families.