Clinical Phenotype and Mutation Spectrum of Alzheimer’s Disease with Causative Genetic Mutation in a Chinese Cohort

doi:10.2174/1567205018666210608120339

摘要

背景：带有致病遗传突变(AD-CGM)的阿尔茨海默病是一种罕见的形式，其特征是异质性的临床表型和受影响的种族群体的基因型变异。目的：系统地描述北京协和医院(PUMCH)队列大样本量下的表型变异和突变谱。方法：对1108例痴呆症患者进行下一代测序(NGS)分析。共纳入40例伴有3例AD基因突变的汉族患者。对所有患者进行了系统回顾，包括临床病史、神经认知评估、脑磁共振成像和脑脊液（脑脊液）生物标志物。结果：我们研究了以下基因突变变异：12个AβPP、13个PSEN1、9个PSEN2和23个新变异。其中大多数为早发性患者，但PSEN1突变携带者的发病年龄最年轻。最常见的症状与AD相似，包括遗忘综合征，其次是精神症状和运动障碍。MRI结果显示，PSEN1和PSEN2突变携带者的顶叶和后颞叶萎缩明显，而AβPP突变携带者有更多的血管变化。脑脊液的生物标志物谱与散发性AD没有明显区分。结论：我们在PUMCH队列的1000多个痴呆患者中发现了一小组AD-CGM受试者，占3.6%。这些受试者通常表现为早发性痴呆，并表现出显著的临床和遗传异质性。鉴定需要使用NGS进行基因突变筛选。虽然家族史通常存在，但我们发现了所有三种基因突变的非家族性病例。

关键词: 阿尔茨海默病，致病遗传突变，下一代测序，表型，淀粉样β前体蛋白，早老蛋白基因，变异。

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DOI https://dx.doi.org/10.2174/1567205018666210608120339	Print ISSN 1567-2050
Publisher Name Bentham Science Publisher	Online ISSN 1875-5828

当代阿耳茨海默病研究

中国队列中阿尔茨海默病的临床表型及突变谱

摘要

当代阿耳茨海默病研究

中国队列中阿尔茨海默病的临床表型及突变谱

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