A novel PSEN2 mutation in amnestic early-onset Alzheimer's disease (EOAD): A familial case series.

IF 2.8 Q2 NEUROSCIENCES

Journal of Alzheimer's disease reports Pub Date : 2025-06-25 eCollection Date: 2025-01-01 DOI:10.1177/25424823251348676

Carl Froilan D Leochico, Ekaterina Rogaeva, Ljubica Zotovic, Ana Luiza Pinto Oliveira, Tina Le, Amit Singnurkar, Mario Masellis, Sara B Mitchell

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Abstract

Familial early-onset Alzheimer's disease (EOAD) is a rare form of dementia often caused by autosomal dominant mutations in APP, PSEN1, or PSEN2. We report a novel PSEN2 missense variant (c.359T > G, p.Ile120Ser) that has been detected in four siblings; three of whom are affected by predominantly amnestic EOAD or mild cognitive impairment in their fifties (supported by neuroimaging biomarkers), while the youngest sibling is currently asymptomatic at age 50. Two of the siblings were also heterozygous for a variant in PSEN1 (c.118_120del, p.Asp40del). Between the two genes, the PSEN2 variant was deemed to be likely pathogenic based on segregation with EOAD, imaging biomarker analyses, and bioinformatic analyses. Reporting genetic findings in familial EOAD cases can help in classifying their pathogenic significance and improving genetic conceptualization within Alzheimer's disease.

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遗忘性早发性阿尔茨海默病（EOAD）中一种新的PSEN2突变：家族病例系列

家族性早发性阿尔茨海默病（EOAD）是一种罕见的痴呆症，通常由APP、PSEN1或PSEN2的常染色体显性突变引起。我们报告了一种新的PSEN2错义变体（c.359T >g, p.Ile120Ser），已在四个兄弟姐妹中检测到；其中三人在50多岁时主要患有遗忘性EOAD或轻度认知障碍（由神经成像生物标志物支持），而最小的兄弟姐妹目前在50岁时无症状。其中两个兄弟姐妹在PSEN1基因变异上也是杂合的（c.118_120del, p.Asp40del）。在这两个基因之间，基于EOAD分离、成像生物标志物分析和生物信息学分析，PSEN2变体被认为可能具有致病性。报告家族性EOAD病例的遗传发现有助于对其致病意义进行分类，并改善阿尔茨海默病的遗传概念。

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来源期刊

Journal of Alzheimer's disease reports

CiteScore

2.80

自引率

0.00%

发文量