父源性中间突变致新发亨廷顿病1例并文献复习  

De novo Huntington′s disease due to paternal intermediate alleles:a case report and literature review

作　　者：黄安琪 梅珊珊[1] 韩妍 杨西西 崔黎黎 王锁彬[1] 董会卿[1] 李存江[1] 林华[1] Huang Anqi;Mei Shanshan;Han Yan;Yang Xixi;Cui Lili;Wang Suobin;Dong Huiqing;Li Cunjiang;Lin Hua(Department of Neurology,Xuanwu Hospital,Capital Medical University,Beijing 100053,China)

机构地区：[1]首都医科大学宣武医院神经内科,北京100053

出　　处：《中华神经科杂志》2023年第9期992-1000,共9页Chinese Journal of Neurology

摘　　要：目的报道1例父代中间突变导致子代新发亨廷顿病患者的临床表现和基因特点。方法回顾性分析1例2022年9月20日就诊于首都医科大学宣武医院的以行走不稳为主诉的无家族史中青年女性患者的临床特征、影像学特点,并按照知情、自愿原则对患者及其父母进行外周血HTT基因检测,并进行相关文献复习。结果患者为38岁女性,症状逐渐进展,主要表现为共济失调、四肢末端的舞蹈样动作、肌张力障碍及认知减退。影像学检查提示双侧尾状核萎缩,双侧尾状核、壳核、局部皮质葡萄糖代谢减低。基因检测结果为HTT基因中存在胞嘧啶-腺瞟呤-鸟嘌呤三核苷酸(CAG)重复序列异常扩增,最终确诊为亨廷顿病。患者及其父亲(67岁)、母亲(62岁)的HTT基因CAG重复次数分别为17/47(致病)、17/35(中间突变)、17/17(正常)。结论父系中间突变异常扩增可导致家族内首发亨廷顿病,因此对临床怀疑亨廷顿病,即使无家族史,均应对患者及其父母进行HTT基因检测,防止临床漏诊及误诊。Objective To report the clinical manifestation and genetic characteristics of a case of de novo Huntington′s disease due to paternal intermediate alleles.Methods Clinical data and imaging features of a middle-aged female,who complained of unstable walking without positive family history and was admitted to Xuanwu Hospital,Capital Medical University on September 20,2022,were retrospectively analyzed.The serum samples of the patient and her parents were used to screen HTT gene dynamic mutation in accordance with the principle of informed consent and voluntary.And the relevant literatures were reviewed.Results This is a 38-year-old female with progressive course,who presented as ataxia,involuntary movement at the end of extremities,dystonia,and cognitive impairment.Imaging results showed atrophy of bilateral caudate nuclei,as well as decreased glucose metabolism of bilateral caudate nuclei,putamen and partial cortex.Genetic testing showed the abnormal expansion of polymorphic trinucleotide(CAG)repeats in HTT gene and confirmed the diagnosis of Huntington′s disease.The CAG repeat length of the patient was 17/47(pathopoiesis),of the father was 17/35(intermediate alleles),and of the mother was 17/17(normal).Conclusions Paternal intermediate alleles may cause the first case of Huntington′s disease in a family.Importantly,HTT gene screening should be performed for the patient and parents when the diagnosis of Huntington′s disease is clinically possible despite negative family history,to prevent the misdiagnosis.

关 键 词：亨廷顿病 三核苷酸重复扩增 中间突变 不自主运动 HTT基因 

分 类 号：R742[医药卫生—神经病学与精神病学]