C9orf72基因突变额颞叶痴呆1家系  

A family case of C9orf72 gene mutation-related frontotemporal dementia

作　　者：周华荣[1] 许丹燕 方雅秀 欧阳聪[1] 张舒维 宁玉萍[1] Zhou Huarong;Xu Danyan;Fang Yaxiu;Ouyang Cong;Zhang Shuwei;Ning Yuping(Geriatric Neuroscience Center,the Affiliated Brain Hospital,Guangzhou Medical University,Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China,Guangzhou Medical University,Guangzhou 510370,China)

机构地区：[1]广州医科大学附属脑科医院老年神经科学中心,广东省神经科学疾病研究重点实验室,神经致病基因与离子通道病省部共建重点实验室,广州510370

出　　处：《中华精神科杂志》2024年第10期678-681,共4页Chinese Journal of Psychiatry

基　　金：广州市科技计划项目(2023A03J0853,2023A03J0827);广州市荔湾区科技计划(202201003);广州市医学重点学科(2021-2023);广州市中医药和中西医结合科技项目(20232A010014)。

摘　　要：额颞叶痴呆是一种神经退行性疾病,表现为进行性精神行为异常,执行功能障碍和语言损害。额颞叶痴呆首次发作症状复杂多样,容易被误诊,且有明显的遗传倾向。C9orf72基因的重复扩增是额颞叶痴呆常见遗传原因,但临床报道较少。本文报道1例老年男性,以渐进性记忆减退起病,初次诊断为阿尔茨海默病。患者有明确家族史,但完善全外显子组检测却未发现明确致病突变。患者妹妹以性格改变及语言功能障碍起病,提示额颞叶痴呆可能,遂完善C9orf72基因动态突变检测,结果发现患者及其妹妹C9orf72基因1号内含子GGGGCC重复次数异常,2例患者最终被诊断为C9orf72基因突变额颞叶痴呆。基于本家系的报道,对于家族性痴呆患者,当全外显子组测序阴性时,建议继续完善C9orf72重复扩增检测。Frontotemporal dementia(FTD)is a neurodegenerative disease characterized by progressive mental and behavioral abnormalities,executive dysfunction,and language impairment.The initial symptoms of FTD are complex and diverse,which can be easily misdiagnosed,and there is an apparent genetic predisposition.Repeated expansion of chromosome 9 open reading frame 72(C9orf72)is a common genetic cause of FTD,but it is rarely reported.In this paper,we report a case of an elderly man with progressive memory loss,initially diagnosed as Alzheimer′s disease.The patient had a definite family history,but whole exome sequencing testing refinement revealed no apparent pathogenic mutation.The patient′s sister exhibited personality changes and language dysfunction,suggesting the possibility of frontotemporal dementia.The patient and her sister were tested for dynamic mutations in the C9orf72,and the results showed that the patient and her sister had an abnormal number of repeats in intron 1,GGGGCC,of the C9orf72.Both were ultimately diagnosed with frontotemporal dementia with C9orf72 mutation.Based on the report of this family,continued refinement of C9orf72 repeat expansion testing is recommended for familial dementia patients if whole exome sequencing is negative.

关 键 词：痴呆 遗传学 家族性痴呆 C9orf72基因 动态突变 

分 类 号：R749.13[医药卫生—神经病学与精神病学]