四川省亨廷顿病家系临床特点、基因诊断与家系分析☆

摘要

Objective To investigate the clinical characteristics of families with Huntington disease in Sichuan, and to make genetic diagnosis and pedigree analysis, and to provide genetic counseling for family members. Methods The detailed clinical data of Huntington disease patients and some family members who visited were collected from provincial people's Hospital of Sichuan between March 2016 and March 2018. The CAG trinucleotide repeats of IT15 gene were examined. The mini mental state examination (MMSE), Montreal cognitive scale (MoCA) were used to evaluate the cognitive function. Hamilton anxiety scale (HAMA), Hamilton Depression scale (HAMD) were used to evaluate the emotion. Activities of daily living scale (ADL) were used to evaluate the ability of daily life. Results Genetic test was conducted on twenty-four individuals from 4 families. Genetic test detected eight HD patients with 41-54 CAG repeats (46.75±4.03) and seven presymptomatic patients with 43~58 CAG repeats (50.00 ±6.40). Four of HD patients required genetic counseling for marriage and childbearing. The number of normal CAG repeats was 12~24, with 17 and 20 being the most common. Correlation analysis found that the number of CAG repeats was negatively correlated with the age of onset (r=-0.967, P＜0.01). ADL score was positively correlated with course of disease (r=0.842, P＜0.01), and negatively correlated with MMSE score (r=-0.930, P＜0.01) and MoCA score (r=-0.932, P＜0.01). Conclusion Genetic test is of great significance in the diagnosis of Huntington's disease, especially in patients with negative family history. The number of CAG repeats is increase from generation to generation and there is genetic anticipation in HD families. The number of CAG repeats can predict the onset age to some extent. Genetic counseling and prenatal diagnosis are important to avoid the birth of a child with HD.%目的 探讨四川地区亨廷顿病(Huntington disease,HD)家系的临床特点,并进行基因诊断及家系分析,同时为家系成员提供遗传咨询.方法 连续收集2016年3月至2018年3月至四川省人民医院就诊的亨廷顿病患者及部分家系成员的详细临床资料,并进行IT15基因CAG三核苷酸重复次数的检测.采用简易智力状态检查量表(Mini-mental state examination, MMSE)、蒙特利尔认知量表(Montreal cognitive assessment, MoCA)、汉密尔顿焦虑量表(Hamilton anxiety scale, HAMA)、汉密尔顿抑郁量表(Hamilton depression scale, HAMD)、日常生活能力量表(activity of daily living scale, ADL)对参与者的认知、情绪及日常生活进行评估,并进行相关分析.结果 4个家系中共有24例参加基因测序,基因确诊患者8例, CAG重复次数在41~54(46.75±4.03)次,发现症状前患者7例,CAG重复次数在43~58(50.00±6.40)次,共有4例有婚育需要.正常CAG重复次数在12~24,以17、20最常见.相关分析发现CAG重复次数与发病年龄呈负相关(r=-0.967,P＜0.01);ADL评分与病程(r=0.842, P＜0.01)呈正相关,与MMSE评分(r=-0.930, P＜0.01)、MoCA评分(r=-0.932, P＜0.01)呈负相关.结论 基因检测对亨廷顿病的诊断有重要意义,特别是对家族史阴性的患者.家系在传代过程中存在CAG重复次数的扩增, 且有遗传早现现象. CAG重复次数在一定程度上能够预测发病年龄的早晚.遗传咨询及产前诊断对避免患儿的出生非常重要.