苏凤娟曾译萱△裴中△梁秀龄△李洵桦△　Jean-Marc Burgunder

12个亨廷顿病家系的临床特点及家系分析

苏凤娟*曾译萱*△裴中*△梁秀龄*△李洵桦*△Jean-Marc Burgunder◎

目的探讨亨廷顿病的临床症状、突变基因以及家系中遗传规律等。方法 收集2013-2014年至中山大学附属第一医院就诊的亨廷顿病患者，绘制完整的家谱图并记录详细的临床资料。对每位患者予IT15基因诊断。对其症状改变，UHDRS评分、行为学进行评估。结果 2013年1月至2014年12月共收治12个亨廷顿病家庭，12例先证者中有2例处于症状前状态，1例青少年亨廷顿病患儿。所有确诊患者的IT15突变基因的CAG重复序列大多在40～60之间，已发病患者的起病年龄13～54岁不等。其家系分析中发现，父系遗传有遗传早现现象。12例家系中，发病晚期的患者有较典型的舞蹈症状、智能减退、精神症状的临床表现，早期发病患者临床症状多变，或以情绪与智能损害为首发症状。结论 晚期亨廷顿病患者临床表现较典型，但早期亨廷顿病的症状多样且不典型，临床诊断困难，行为学改变，影像学检查有重要的参考价值，基因诊断是该疾病确诊的重要方式。

亨廷顿病基因诊断影像学行为问题

【Abstract】Objective To investigate the clinical manifestation，inherited pattern and the related factor of Huntington disease families.Method The clinical data from 12 HD families was collected from 2013-2014.Patients received the genetic test and neurological evaluation including motor，cognitive and problem of behavior.Results There were 12 patients having the IT15 gene dynamic mutations，including 1 Juvenile Huntington disease patient and 3 pre-symptomatic mutant gene carriers.The average CAG repeats of these patients was between the range of 40 to 60，and the average onset age ranged from 13 to 54 year-old.Positive family history and genetic anticipation could be observed.Patients presented with different clinical manifestations at the early stage while had typical chorea movements，declined cognitive and psychiatric symptoms at the late stage of the illness.Conclusions There are typical triad symptoms in the late stage but not in the early stage nor pre-symptom stage illness.Clinical manifestation and the neuroimaging are both of great reference value，and the genetic test is essential for final diagnosis.

【Key Words】Huntington disease Genetic testNeuroimaging Behavior problem

亨廷顿病（Huntington disease，HD）是常染色体显性遗传性疾病。最早于1872年由美国医生George Huntington报道。HD是一种基底核和大脑皮质的变性疾病，其病变基因位于4p16.3中IT15基因上［1］的一段多态性的三核苷酸（又称三联体triplet）CAG的异常重复序列：CAG拷贝数在正常人群中为11～34，平均为19，但在患者中异常增多可达42～100个。临床症状上，HD患者多在成年后发病，有特征性的舞蹈样症状［2-3］，即突然发生的、过度的、自发的并且持续存在的舞蹈样动作以及肌张力障碍等运动障碍，症状慢性进行性加重。……