亨廷顿舞蹈病的临床特征及基因分析

Clinical and genetic features of Huntington's disease

目的研究亨廷顿舞蹈病(HD)患者的临床特征和遗传学特点,并探讨基因型和临床表型相关性。方法收集45个亨廷顿舞蹈病家系临床资料,并采用简易精神状态评价量表(MMSE)对HD患者及其家系成员的精神状态进行评分。使用聚合酶链式反应(PCR)扩增HTT基因1号外显子,再进行毛细管电泳片段分析。对取得的数据进行处理和分析。结果 HTT基因检测阳性[(CAG) n拷贝数大于39次]共56人,其中35人已发病,21人为症状前患者。患者平均发病年龄(39. 34±10. 93)岁。首发症状均为舞蹈样动作,部分患者伴有精神行为异常、认知功能障碍的组合形式同时出现。认知功能评估在不同病程组比较差异有统计学意义(P <0. 05)。发病年龄和HTT基因CAG病理拷贝数呈负相关(r=-0. 769,P=0. 000)。结论 HD是一种具有高度临床异质性和遗传异质性的神经变性疾病。发病年龄越早HTT基因CAG病理拷贝数越高,反之越低。患者认知功能与病程密切相关,病程越长,认知功能障碍越易产生。精神行为异常最常见的表现为易激惹。

Objective To investigate the clinical and genetic features of patients with Huntington＇s disease （HD） and the association between genotype and clinical phenotype. Methods Related clinical data were collected from 45 families with HD, and the Mini-mental State Examination （MMSE） was used to determine the scores of mental state of HD patients and their family members. PCR was used to amplify exon 1 of the HTT gene and then capillary electrophoresis was used for fragment analysis. The data obtained were analyzed. Results A total of 56 individuals were found to have positive HTT gene （CAG repeats 〉39 times）, among whom 35 had already developed HD and 21 were in the presymptomatic state. The mean age of onset was 39.34±10.93 years. The initial symptom was involuntary dance-like movements in all patients, and some patients also had mental and behavioral disorders and cognitive impairment. There was a significant difference in cognitive function assessment between the groups of patients with different durations of disease （P〈0.05）. Age of onset was negatively correlated with the number of CAG repeats in the HTT gene （r=-0.769, P=0.000）. Conclusions HD is a neurodegenerative disease with high clinical and genetic heterogeneity. Age of onset is negatively correlated with the number of CAG repeats in the HTT gene. The patient＇s cognitive function is closely associated with the course of the disease. Patients with a longer course of disease are more likely to develop cognitive impairment. Irritability is the most common mental and behavioral disorder.