一个多巴胺反应性肌张力障碍家系的临床表型及GCH1基因突变分析

Analysis of clinical phenotype and CGH1 gene mutations in a family affected with dopa-responsive dystonia

目的探讨1个多巴胺反应性肌张力障碍家系（dopa-responsive dystonias，DRD）的GCH1基因突变及临床特征。方法应用聚合酶链反应结合测序技术对1个家系的7名成员进行GCH1基因突变分析。结果测序结果显示家系中先证者及其一兄一妹和母亲的GCH1基因存在c．550C〉T杂合突变。3例患者发病年龄为13～60岁，病情进展慢，晨轻暮重，主要表现为下肢的肌张力障碍、手抖动，对小剂量多巴制剂反应较好，先证者母亲尚未发病。软件分析显示c．550C〉T可能为一致病突变。结论C．550C〉T突变可能是该家系的致病原因。DRD家系中，携带C．550C〉T突变的患者可以有不同的临床表型，发病年龄可以有早有晚，甚至可能终身不发病。

Objective To explore genetic mutations and clinical features of a pedigree affected with dopa-responsive dystonia. Methods PCR and Sanger sequencing were applied to detect mutations of the GCH1 gene among 7 members from the pedigree. Results The family was detected to have a known heterozygous mutation of the GCH1 gene （c. 550C〉T）. For the 7 members from the pedigree, the age of onset has ranged from 13 to 60 years. The mother of the proband has carried the same mutation but was still healthy at 80. The symptoms of the other three patients were in slow progression, with diurnal fluctuation which can be improved with sleeping, dystonias of lower limbs, and tremor of both hands. Treatment with small dose of levodopa has resulted in significant improvement of clinical symptoms. By database analysis, the c. 550C〉T mutation was predicted as probably pathological. Conclusion The c. 550C〉T mutation probably underlies the disease in this pedigree. The clinical phenotypes of family members may be variable for their ages of onset. Some may even be symptom free.