Cargando…

A Possible Pathogenic PSEN2 Gly56Ser Mutation in a Korean Patient with Early-Onset Alzheimer’s Disease

Early-onset Alzheimer’s disease (EOAD) is characterized by the presence of neurological symptoms in patients with Alzheimer’s disease (AD) before 65 years of age. Mutations in pathological genes, including amyloid protein precursor (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2), were associat...

Descripción completa

Detalles Bibliográficos
Autores principales: Shim, Kyu-Hwan, Kang, Min-Ju, Bae, Heewon, Kim, Danyeong, Park, Jiwon, An, Seong-Soo A., Jeong, Da-Eun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8953053/
https://www.ncbi.nlm.nih.gov/pubmed/35328387
http://dx.doi.org/10.3390/ijms23062967
_version_ 1784675757180583936
author Shim, Kyu-Hwan
Kang, Min-Ju
Bae, Heewon
Kim, Danyeong
Park, Jiwon
An, Seong-Soo A.
Jeong, Da-Eun
author_facet Shim, Kyu-Hwan
Kang, Min-Ju
Bae, Heewon
Kim, Danyeong
Park, Jiwon
An, Seong-Soo A.
Jeong, Da-Eun
author_sort Shim, Kyu-Hwan
collection PubMed
description Early-onset Alzheimer’s disease (EOAD) is characterized by the presence of neurological symptoms in patients with Alzheimer’s disease (AD) before 65 years of age. Mutations in pathological genes, including amyloid protein precursor (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2), were associated with EOAD. Seventy-six mutations in PSEN2 have been found around the world, which could affect the activity of γ-secretase in amyloid beta processing. Here, a heterozygous PSEN2 point mutation from G to A nucleotide change at position 166 (codon 56; c.166G>A, Gly56Ser) was identified in a 64-year-old Korean female with AD with progressive cognitive memory impairment for the 4 years prior to the hospital visit. Hippocampal atrophy was observed from magnetic resonance imaging-based neuroimaging analyses. Temporal and parietal cortex hypometabolisms were identified using fluorodeoxyglucose positron emission tomography. This mutation was at the N-terminal portion of the presenilin 2 protein on the cytosolic side. Therefore, the serine substitution may have promoted AD pathogenesis by perturbing to the mutation region through altered phosphorylation of presenilin. In silico analysis revealed that the mutation altered protein bulkiness with increased hydrophilicity and reduced flexibility of the mutated region of the protein. Structural changes were likely caused by intramolecular interactions between serine and other residues, which may have affected APP processing. The functional study will clarify the pathogenicity of the mutation in the future.
format Online
Article
Text
id pubmed-8953053
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-89530532022-03-26 A Possible Pathogenic PSEN2 Gly56Ser Mutation in a Korean Patient with Early-Onset Alzheimer’s Disease Shim, Kyu-Hwan Kang, Min-Ju Bae, Heewon Kim, Danyeong Park, Jiwon An, Seong-Soo A. Jeong, Da-Eun Int J Mol Sci Communication Early-onset Alzheimer’s disease (EOAD) is characterized by the presence of neurological symptoms in patients with Alzheimer’s disease (AD) before 65 years of age. Mutations in pathological genes, including amyloid protein precursor (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2), were associated with EOAD. Seventy-six mutations in PSEN2 have been found around the world, which could affect the activity of γ-secretase in amyloid beta processing. Here, a heterozygous PSEN2 point mutation from G to A nucleotide change at position 166 (codon 56; c.166G>A, Gly56Ser) was identified in a 64-year-old Korean female with AD with progressive cognitive memory impairment for the 4 years prior to the hospital visit. Hippocampal atrophy was observed from magnetic resonance imaging-based neuroimaging analyses. Temporal and parietal cortex hypometabolisms were identified using fluorodeoxyglucose positron emission tomography. This mutation was at the N-terminal portion of the presenilin 2 protein on the cytosolic side. Therefore, the serine substitution may have promoted AD pathogenesis by perturbing to the mutation region through altered phosphorylation of presenilin. In silico analysis revealed that the mutation altered protein bulkiness with increased hydrophilicity and reduced flexibility of the mutated region of the protein. Structural changes were likely caused by intramolecular interactions between serine and other residues, which may have affected APP processing. The functional study will clarify the pathogenicity of the mutation in the future. MDPI 2022-03-09 /pmc/articles/PMC8953053/ /pubmed/35328387 http://dx.doi.org/10.3390/ijms23062967 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Shim, Kyu-Hwan
Kang, Min-Ju
Bae, Heewon
Kim, Danyeong
Park, Jiwon
An, Seong-Soo A.
Jeong, Da-Eun
A Possible Pathogenic PSEN2 Gly56Ser Mutation in a Korean Patient with Early-Onset Alzheimer’s Disease
title A Possible Pathogenic PSEN2 Gly56Ser Mutation in a Korean Patient with Early-Onset Alzheimer’s Disease
title_full A Possible Pathogenic PSEN2 Gly56Ser Mutation in a Korean Patient with Early-Onset Alzheimer’s Disease
title_fullStr A Possible Pathogenic PSEN2 Gly56Ser Mutation in a Korean Patient with Early-Onset Alzheimer’s Disease
title_full_unstemmed A Possible Pathogenic PSEN2 Gly56Ser Mutation in a Korean Patient with Early-Onset Alzheimer’s Disease
title_short A Possible Pathogenic PSEN2 Gly56Ser Mutation in a Korean Patient with Early-Onset Alzheimer’s Disease
title_sort possible pathogenic psen2 gly56ser mutation in a korean patient with early-onset alzheimer’s disease
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8953053/
https://www.ncbi.nlm.nih.gov/pubmed/35328387
http://dx.doi.org/10.3390/ijms23062967
work_keys_str_mv AT shimkyuhwan apossiblepathogenicpsen2gly56sermutationinakoreanpatientwithearlyonsetalzheimersdisease
AT kangminju apossiblepathogenicpsen2gly56sermutationinakoreanpatientwithearlyonsetalzheimersdisease
AT baeheewon apossiblepathogenicpsen2gly56sermutationinakoreanpatientwithearlyonsetalzheimersdisease
AT kimdanyeong apossiblepathogenicpsen2gly56sermutationinakoreanpatientwithearlyonsetalzheimersdisease
AT parkjiwon apossiblepathogenicpsen2gly56sermutationinakoreanpatientwithearlyonsetalzheimersdisease
AT anseongsooa apossiblepathogenicpsen2gly56sermutationinakoreanpatientwithearlyonsetalzheimersdisease
AT jeongdaeun apossiblepathogenicpsen2gly56sermutationinakoreanpatientwithearlyonsetalzheimersdisease
AT shimkyuhwan possiblepathogenicpsen2gly56sermutationinakoreanpatientwithearlyonsetalzheimersdisease
AT kangminju possiblepathogenicpsen2gly56sermutationinakoreanpatientwithearlyonsetalzheimersdisease
AT baeheewon possiblepathogenicpsen2gly56sermutationinakoreanpatientwithearlyonsetalzheimersdisease
AT kimdanyeong possiblepathogenicpsen2gly56sermutationinakoreanpatientwithearlyonsetalzheimersdisease
AT parkjiwon possiblepathogenicpsen2gly56sermutationinakoreanpatientwithearlyonsetalzheimersdisease
AT anseongsooa possiblepathogenicpsen2gly56sermutationinakoreanpatientwithearlyonsetalzheimersdisease
AT jeongdaeun possiblepathogenicpsen2gly56sermutationinakoreanpatientwithearlyonsetalzheimersdisease