摘要： 目的 报道1例伴PSEN2基因V214L突变的早发型阿尔茨海默病患者的临床表型和基因变异特点，并进行家系分析。方法与结果 男性先证者，58岁发病，病程5年，以记忆力减退为首发表现，症状进行性加重，无痴呆家族史。简易智能状态检查量表评分1分，蒙特利尔认知评价量表评分为零，日常生活活动能力量表评分71分，Hachinski缺血评分3分。头部MRI显示大脑皮质广泛萎缩，以双侧海马萎缩显著，深部脑白质多发高信号（Fazekas分级2级）。痴呆相关基因外显子高通量测序显示，先证者及其妹均存在PSEN2基因第8号外显子c.640G > T（p.V214L）杂合错义突变和SORL1基因第28号外显子c.3815-4A > C杂合剪接突变。先证者最终诊断为伴PSEN2基因V214L突变的早发型阿尔茨海默病，其妹考虑为阿尔茨海默病绝对风险人群，该家系明确为早发型阿尔茨海默病家系。结论 PSEN2基因V214L突变很可能导致早发型阿尔茨海默病，尚待研究证实该突变对β-淀粉样蛋白40和42的影响以验证其致病性。

关键词: 阿尔茨海默病, 早老素2, 基因, 突变, 系谱

Abstract: Objective To report clinical phenotype and gene mutation characteristics of one case of early-onset Alzheimer's disease (EOAD) associated with PSEN2 V214L mutation and conduct a pedigree analysis. Methods and Results A 63-year-old male proband with no family history of dementia, onset at 58 years old, had memory loss as the first manifestation and progressive aggravation of symptoms. Neuropsychological tests showed a score of 1 on Mini-Mental State Examination (MMSE), 0 on Montreal Cognitive Assessment (MoCA), 71 on Activities of Daily Living Scale (ADL), and 3 on Hachinski Ischemic Score (HIS). Head MRI revealed extensive cortical atrophy, with prominent atrophy of bilateral hippocampal, multiple hyperintensity in deep white matter (Fazekas grade 2). Exons of high-throughput sequencing of dementia-related genes showed that both the proband and his sister had heterozygous missense mutations in exon 8 of PSEN2 gene c.640G > T (p.V214L) and heterozygous splicing mutations in exon 28 of SORL1 gene c. 3815-4A > C. The proband was finally diagnosed with EOAD associated with PSEN2 V214L mutation, and the proband's sister was considered as an absolute risk group for Alzheimer's disease (AD). Conclusions The PSEN2 V214L mutation probably causes EOAD. Further investigations should be conducted to evaluate the effects on the production of amyloid β-protein 40 and 42 (Aβ₄₀ and Aβ₄₂), then verify its pathogenicity.

Key words: Alzheimer disease, Presenilin-2, Genes, Mutation, Pedigree