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A Novel Probable Pathogenic PSEN2 Mutation p.Phe369Ser Associated With Early-Onset Alzheimer's Disease in a Chinese Han Family: A Case Report

The pathogenesis of Alzheimer's disease is complex, and early-onset Alzheimer's disease (EOAD) is mostly influenced by genetic factors. Presenilin-1, presenilin-2 (PSEN2), and amyloid precursor protein are currently known as the three main causative genes for autosomal dominant EOAD, with...

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Autores principales: Wan, Ke, Ma, Zhen-Juan, Zhou, Xia, Zhang, Yi-Mei, Yu, Xian-Feng, You, Meng-Zhe, Huang, Chao-Juan, Zhang, Wei, Sun, Zhong-Wu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8334358/
https://www.ncbi.nlm.nih.gov/pubmed/34366829
http://dx.doi.org/10.3389/fnagi.2021.710075
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author Wan, Ke
Ma, Zhen-Juan
Zhou, Xia
Zhang, Yi-Mei
Yu, Xian-Feng
You, Meng-Zhe
Huang, Chao-Juan
Zhang, Wei
Sun, Zhong-Wu
author_facet Wan, Ke
Ma, Zhen-Juan
Zhou, Xia
Zhang, Yi-Mei
Yu, Xian-Feng
You, Meng-Zhe
Huang, Chao-Juan
Zhang, Wei
Sun, Zhong-Wu
author_sort Wan, Ke
collection PubMed
description The pathogenesis of Alzheimer's disease is complex, and early-onset Alzheimer's disease (EOAD) is mostly influenced by genetic factors. Presenilin-1, presenilin-2 (PSEN2), and amyloid precursor protein are currently known as the three main causative genes for autosomal dominant EOAD, with the PSEN2 mutation being the rarest. In this study, we reported a 56-year-old Chinese Han proband who presented with prominent progressive amnesia, aphasia, executive function impairment, and depression 5 years ago. The 3-year follow-up showed that the patient experienced progressive brain atrophy displayed on magnetic resonance imaging (MRI) and dramatic cognitive decline assessed by neuropsychological evaluation. This patient was clinically diagnosed as EOAD based on established criteria. A heterozygous variant (NM_000447.2: c.1106T>C) of PSEN2 was identified for the first time in this patient and her two daughters. This mutation causing a novel missense mutation (p.Phe369Ser) in transmembrane domain 7 encoded by exon 11 had not been reported previously in 1000Genomes, ExAC, or ClinVar databases. This mutation was predicted by four in silico prediction programs, which all strongly suggested that it was damaging. Our results suggest that this novel PSEN2 Phe369Ser mutation may alter PSEN2 protein function and associate with EOAD.
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spelling pubmed-83343582021-08-05 A Novel Probable Pathogenic PSEN2 Mutation p.Phe369Ser Associated With Early-Onset Alzheimer's Disease in a Chinese Han Family: A Case Report Wan, Ke Ma, Zhen-Juan Zhou, Xia Zhang, Yi-Mei Yu, Xian-Feng You, Meng-Zhe Huang, Chao-Juan Zhang, Wei Sun, Zhong-Wu Front Aging Neurosci Neuroscience The pathogenesis of Alzheimer's disease is complex, and early-onset Alzheimer's disease (EOAD) is mostly influenced by genetic factors. Presenilin-1, presenilin-2 (PSEN2), and amyloid precursor protein are currently known as the three main causative genes for autosomal dominant EOAD, with the PSEN2 mutation being the rarest. In this study, we reported a 56-year-old Chinese Han proband who presented with prominent progressive amnesia, aphasia, executive function impairment, and depression 5 years ago. The 3-year follow-up showed that the patient experienced progressive brain atrophy displayed on magnetic resonance imaging (MRI) and dramatic cognitive decline assessed by neuropsychological evaluation. This patient was clinically diagnosed as EOAD based on established criteria. A heterozygous variant (NM_000447.2: c.1106T>C) of PSEN2 was identified for the first time in this patient and her two daughters. This mutation causing a novel missense mutation (p.Phe369Ser) in transmembrane domain 7 encoded by exon 11 had not been reported previously in 1000Genomes, ExAC, or ClinVar databases. This mutation was predicted by four in silico prediction programs, which all strongly suggested that it was damaging. Our results suggest that this novel PSEN2 Phe369Ser mutation may alter PSEN2 protein function and associate with EOAD. Frontiers Media S.A. 2021-07-21 /pmc/articles/PMC8334358/ /pubmed/34366829 http://dx.doi.org/10.3389/fnagi.2021.710075 Text en Copyright © 2021 Wan, Ma, Zhou, Zhang, Yu, You, Huang, Zhang and Sun. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Wan, Ke
Ma, Zhen-Juan
Zhou, Xia
Zhang, Yi-Mei
Yu, Xian-Feng
You, Meng-Zhe
Huang, Chao-Juan
Zhang, Wei
Sun, Zhong-Wu
A Novel Probable Pathogenic PSEN2 Mutation p.Phe369Ser Associated With Early-Onset Alzheimer's Disease in a Chinese Han Family: A Case Report
title A Novel Probable Pathogenic PSEN2 Mutation p.Phe369Ser Associated With Early-Onset Alzheimer's Disease in a Chinese Han Family: A Case Report
title_full A Novel Probable Pathogenic PSEN2 Mutation p.Phe369Ser Associated With Early-Onset Alzheimer's Disease in a Chinese Han Family: A Case Report
title_fullStr A Novel Probable Pathogenic PSEN2 Mutation p.Phe369Ser Associated With Early-Onset Alzheimer's Disease in a Chinese Han Family: A Case Report
title_full_unstemmed A Novel Probable Pathogenic PSEN2 Mutation p.Phe369Ser Associated With Early-Onset Alzheimer's Disease in a Chinese Han Family: A Case Report
title_short A Novel Probable Pathogenic PSEN2 Mutation p.Phe369Ser Associated With Early-Onset Alzheimer's Disease in a Chinese Han Family: A Case Report
title_sort novel probable pathogenic psen2 mutation p.phe369ser associated with early-onset alzheimer's disease in a chinese han family: a case report
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8334358/
https://www.ncbi.nlm.nih.gov/pubmed/34366829
http://dx.doi.org/10.3389/fnagi.2021.710075
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