Cargando…
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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1783733052588949504 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8334358 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT wanke anovelprobablepathogenicpsen2mutationpphe369serassociatedwithearlyonsetalzheimersdiseaseinachinesehanfamilyacasereport AT mazhenjuan anovelprobablepathogenicpsen2mutationpphe369serassociatedwithearlyonsetalzheimersdiseaseinachinesehanfamilyacasereport AT zhouxia anovelprobablepathogenicpsen2mutationpphe369serassociatedwithearlyonsetalzheimersdiseaseinachinesehanfamilyacasereport AT zhangyimei anovelprobablepathogenicpsen2mutationpphe369serassociatedwithearlyonsetalzheimersdiseaseinachinesehanfamilyacasereport AT yuxianfeng anovelprobablepathogenicpsen2mutationpphe369serassociatedwithearlyonsetalzheimersdiseaseinachinesehanfamilyacasereport AT youmengzhe anovelprobablepathogenicpsen2mutationpphe369serassociatedwithearlyonsetalzheimersdiseaseinachinesehanfamilyacasereport AT huangchaojuan anovelprobablepathogenicpsen2mutationpphe369serassociatedwithearlyonsetalzheimersdiseaseinachinesehanfamilyacasereport AT zhangwei anovelprobablepathogenicpsen2mutationpphe369serassociatedwithearlyonsetalzheimersdiseaseinachinesehanfamilyacasereport AT sunzhongwu anovelprobablepathogenicpsen2mutationpphe369serassociatedwithearlyonsetalzheimersdiseaseinachinesehanfamilyacasereport AT wanke novelprobablepathogenicpsen2mutationpphe369serassociatedwithearlyonsetalzheimersdiseaseinachinesehanfamilyacasereport AT mazhenjuan novelprobablepathogenicpsen2mutationpphe369serassociatedwithearlyonsetalzheimersdiseaseinachinesehanfamilyacasereport AT zhouxia novelprobablepathogenicpsen2mutationpphe369serassociatedwithearlyonsetalzheimersdiseaseinachinesehanfamilyacasereport AT zhangyimei novelprobablepathogenicpsen2mutationpphe369serassociatedwithearlyonsetalzheimersdiseaseinachinesehanfamilyacasereport AT yuxianfeng novelprobablepathogenicpsen2mutationpphe369serassociatedwithearlyonsetalzheimersdiseaseinachinesehanfamilyacasereport AT youmengzhe novelprobablepathogenicpsen2mutationpphe369serassociatedwithearlyonsetalzheimersdiseaseinachinesehanfamilyacasereport AT huangchaojuan novelprobablepathogenicpsen2mutationpphe369serassociatedwithearlyonsetalzheimersdiseaseinachinesehanfamilyacasereport AT zhangwei novelprobablepathogenicpsen2mutationpphe369serassociatedwithearlyonsetalzheimersdiseaseinachinesehanfamilyacasereport AT sunzhongwu novelprobablepathogenicpsen2mutationpphe369serassociatedwithearlyonsetalzheimersdiseaseinachinesehanfamilyacasereport |