目的 报道1例额颞叶痴呆合并肌萎缩侧索硬化(FTD-ALS)患者,回顾目前报道该病的相关文献,总结FTD-ALS的临床及遗传学特点.方法 报道1例2017年5月就诊于安徽医科大学第一附属医院院的FTD-ALS患者,从患者及其一级亲属外周血提取DNA行遗传学检测.检索已详细报道的国人FTD-ALS病例,对该病的临床及遗传学特点进行总结分析.结果 本例患者为49岁男性,临床表现为反应迟缓、逐渐加重的命名及词汇理解障碍,影像学提示颞叶萎缩;后逐渐出现饮水呛咳、多处肌肉萎缩伴肌束颤动,病理征及原始反射阳性,肌电图提示广泛神经源性改变,符合FTD-ALS诊断标准.在TBK1基因上发现有新发杂合突变(c.1335G＞A chr12:64879792 p.W445X),参考美国医学遗传学和基因组学会相关指南提示该突变变异类型为疑似致病突变,但尚未被人类基因突变数据库报道过.目前国内外共报道有详细资料的中国FTD-ALS患者21例(包含本例),其中男性13例,女性8例,发病年龄(59.01±8.58)(44～73)岁,多数以FTD起病,继而出现ALS.已知有7例完善遗传学检测,其中5例有阳性结果,发生突变的分别为TBK1基因2例,C9orf72、DCTN1、TARDBP基因各1例.多数为散发型FTD-ALS(包含本例),仅2例为家族型FTD-ALS.结论 FTD-ALS较为罕见,多以散发型为主,发病年龄较轻,痴呆以行为变异型FTD为主要表现,认知障碍多先于ALS;除C9orf72之外,TBK1也是FTD-ALS的重要致病基因,遗传学检测对该病诊断具有重要价值.

Objective To report a case of frontotemporal dementia with amyotrophic lateral sclerosis (FTD-ALS),review the relevant literature and then summarize the clinical and genetic characteristics of FTD-ALS patients.Methods A FTD-ALS patient admitted to the First Affiliated Hospital,Anhui Medical University in May 2017.After diagnosis,genetic analyses were performed on DNA extracted from peripheral blood of the patient and his first-degree relatives.Chinese FTD-ALS patients reported in detail were reviewed and the clinical and genetic characteristics of the disease were summarized.Results The patient,a 49-year-old man,responded slowly with impaired confrontation naming and impaired single-word comprehension.Magnetic resonance imaging showed temporal lobe atrophy.Besides,the patient gradually developed atrophy in limbs and bulbar muscles as well as spasticity of arms and legs,with positive pathological and primitive reflexes.Electromyography suggested a wide range of neurogenic changes,which were consistent with the FTD-ALS diagnostic criteria.A new heterozygous mutation (c.1335G＞A chr12:64879792 p.W445X) was found in the TBK1 gene.The reference to the American College of Medical Genetics and Genomics guidelines suggested that this mutation type is likely pathogenic,which has not been reported by the Human Gene Mutation Database.There were a total of 21 Chinese FTD-ALS patients (including this case) reported in detail,including 13 males and eight females.The age of onset was (59.01±8.58) (44-73) years.Most of them had typical manifestations of FTD as the first symptom,followed by ALS.Among these patients,seven had genetic data analyses,five of which had positive results.The mutations occurred in TBK1 (two cases),C9onf72 (one case),DCTN1 (one case) and TARDBP (one case)genes,respectively.Most FTD-ALS cases were sporadic (including this case),and only two cases were familial.Conclusions FTD-ALS is a relatively rare disease,mostly sporadic,with a younger onset age,in which behavioral variant FTD is the main manifestation of dementia in the context of ALS,and cognitive impairment is occurred earlier than ALS.In addition to C9orf72 gene,TBK1 gene is an important pathogenic gene of FTD-ALS.Genetic analysis is of great value in the early diagnosis of FTD-ALS.