摘要目的 探讨1个中国家族性早发型阿尔茨海默病家系的临床表现、基因突变及影像学表现.方法 收集2016年10月11日就诊于我院神经内科、临床诊断为早发型阿尔茨海默病的先证者及其家系,对先证者进行早老素1基因、早老素2基因、微管相关蛋白tau基因、β淀粉样前体蛋白基因检测,分析其临床表现及辅助检查、神经心理测评结果,并对家系中部分成员、50例散发性阿尔茨海默病患者和50名家系外正常个体进行突变位点验证.结果 该家系先证者表现为语言损害、记忆力下降、人格改变、言语重复、视空间障碍、精神行为异常.我们通过基因检测发现先证者早老素1基因7号外显子第226位点密码子发生p.L226R突变,家系中另5位成员(Ⅲ1、Ⅲ2、Ⅲ4、Ⅲ6、Ⅲ7)亦存在该位点的突变.先证者母亲有可疑症状,姐姐及弟弟与先证者有相似症状,均已去世.50例散发性阿尔茨海默病患者和50名家系外正常个体均未发现该突变.先证者CT血管造影示血管正常,18氟-脱氧葡萄糖-正电子发射体层显像(18F-FDG-PET)显示脑萎缩及双侧额叶、颞叶、顶叶、海马代谢减低;2例携带者(Ⅲ6、Ⅲ7)MRI、MRA、18 F-FDG-PET均正常.结论 我们在中国人群中发现了早期以语言损害为主要表现的家族性早发型阿尔茨海默病的1个突变位点,即早老素1基因第7号外显子p.L226R突变,此突变很可能与该家系的发病相关.

abstractsObjective To analyze the clinical presentation , the mutation of the pathogenic genes and imaging features in a Chinese Han early-onset Alzheimer's disease pedigree.Methods A pedigree of Alzheimer's disease was collected.The DNA sequence of presenilin 1 (PSEN1), presenilin 2, micro-tubule associated protein tau ,β-amyloid precursor protein gene was analyzed , the clinical presentation , results of accessory examination , neuropsychological evaluation of the proband were investigated and the point mutations of some members of the family , 50 sporadic Alzheimer's disease patients , 50 normal controls were verified.Results The proband of the family appeared as language impairment , memory loss, personality change, repeated language, visuospatial impairment, mental and behavior disorder.The gene detection showed p.L226R mutation in the condon 226 in the exon 7 of PSEN1 gene of the proband and five other family members (Ⅲ1 ,Ⅲ2 ,Ⅲ4 ,Ⅲ6 ,Ⅲ7 ).The mother of the proband had the suspicious symptoms , and the sister and the brother of the proband had the similiar symptoms with the proband , all of whom died.Fifty sporadic Alzheimer'disease patients and 50 unrelated normal subjects did not have the mutation .The computed tomographic angiography showed that the brain blood vessels were normal and 18 F-fludeoxyglucose positron emission tomography (18F-FDG-PET) showed brain atrophy and hypometabolism in frontotemporal regions, parietal regions, hippocampal areas, however, the MRI, MRA and 18F-FDG-PET of the two mutation carriers (Ⅲ6 ,Ⅲ7 ) were all normal.Conclusion We reported a novel mutation in an early-onset Alzheimer's disease family presented as language impairment in the early stage of the disease , the p.L226R mutation of PSEN1, which may be a pathogenic mutation to cause the family's dementia.