舞蹈病家系临床、影像学特征及基因突变分析

Clinical,neuroimaging features and mutation analysis of genes in a large Chinese pedigree of chorea

目的明确一个无明显痴呆的舞蹈病家系的临床、影像学特征及IT15、DRPLA、JPH3、TBP基因突变情况。方法对5例已发病患者的临床及脑影像学特征进行分析;用聚合酶链反应技术、8%变性聚丙烯酰胺凝胶电泳及直接测序等方法,对18名家系成员的IT15、DRPLA、JPH3、TBP基因的三核苷酸(CAG/CTG)重复序列进行分析。结果5例患者主要表现为舞蹈样不自主运动;3例患者头颅磁共振成像无明显尾状核萎缩,其中1例头颅单光子发射计算机断层显像(SPECT)提示双侧基底节血流受损,比健康人血流灌注减少;检测到9例(5例患者,4例症状前患者)分别有一(CAG)n重复拷贝数大于40次的IT15基因,无DRPLA、JPH3、TBP基因的突变。结论根据临床和影像学特征该家系在临床上不能确诊为亨廷顿舞蹈病,但经基因突变分析确定了IT15基因中(CAG)n重复拷贝数的异常扩展导致该家系发生了亨廷顿舞蹈病。

Objective To study the clinical, neuroimaging features and identify the mutations of IT15,DRPLA,JPH3 and TBP genes in a large Chinese family of chorea. Methods Five patients were assessed according to their clinical and neuroimaging features. Genomic DNA of 18 family individuals was used for amplification of the CAG/CTG repeats of IT15,DRPLA,JPH3 and TBP genes by polymerase chain reactioh （PCR）. The numbers of CAG/CTG were determined by electrophoreses through an 8% denaturing polyacrylamide gel and direct sequence analysis. Results The main symptoms of 5 patients were involuntary movements. MRI scans showed no obvious caudate atrophy in three patients. While the proband showed basal ganglia blood flow was reduced following the SPECT scan. Total 9 out of 18 family members had more than 40 CAG repeats in the IT15 gene （5 patients and 4 asymptomatic）, but no mutation was detected in the DRPLA,JPH3 and TBP genes in 18 family members. Conclusions Huntington disease （ HD ）, HD can not be made a definite diagnosis on basis of clinical and neuroimaging features. The CAG expansion at the IT15 gene by mutation analysis might provide us the valuable insights in HD.