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Analysis of 50 Neurodegenerative Genes in Clinically Diagnosed Early-Onset Alzheimer’s Disease

Alzheimer’s disease (AD), Parkinson’s disease (PD), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), and prion diseases have a certain degree of clinical, pathological, and molecular overlapping. Previous studies revealed that many causative mutations in...

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Autores principales: Giau, Vo Van, Senanarong, Vorapun, Bagyinszky, Eva, An, Seong Soo A., Kim, SangYun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471359/
https://www.ncbi.nlm.nih.gov/pubmed/30917570
http://dx.doi.org/10.3390/ijms20061514
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author Giau, Vo Van
Senanarong, Vorapun
Bagyinszky, Eva
An, Seong Soo A.
Kim, SangYun
author_facet Giau, Vo Van
Senanarong, Vorapun
Bagyinszky, Eva
An, Seong Soo A.
Kim, SangYun
author_sort Giau, Vo Van
collection PubMed
description Alzheimer’s disease (AD), Parkinson’s disease (PD), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), and prion diseases have a certain degree of clinical, pathological, and molecular overlapping. Previous studies revealed that many causative mutations in AD, PD, and FTD/ALS genes could be found in clinical familial and sporadic AD. To further elucidate the missing heritability in early-onset Alzheimer’s disease (EOAD), we genetically characterized a Thai EOAD cohort by Next-Generation Sequencing (NGS) with a high depth of coverage, capturing variants in 50 previously recognized AD and other related disorders’ genes. A novel mutation, APP p.V604M, and the known causative variant, PSEN1 p.E184G, were found in two of the familiar cases. Remarkably, among 61 missense variants were additionally discovered from 21 genes out of 50 genes, six potential mutations including MAPT P513A, LRRK2 p.R1628P, TREM2 p.L211P, and CSF1R (p.P54Q and pL536V) may be considered to be probably/possibly pathogenic and risk factors for other dementia leading to neuronal degeneration. All allele frequencies of the identified missense mutations were compared to 622 control individuals. Our study provides initial evidence that AD and other neurodegenerative diseases may represent shades of the same disease spectrum, and consideration should be given to offer exactly embracing genetic testing to patients diagnosed with EOAD. Our results need to be further confirmed with a larger cohort from this area.
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spelling pubmed-64713592019-04-26 Analysis of 50 Neurodegenerative Genes in Clinically Diagnosed Early-Onset Alzheimer’s Disease Giau, Vo Van Senanarong, Vorapun Bagyinszky, Eva An, Seong Soo A. Kim, SangYun Int J Mol Sci Article Alzheimer’s disease (AD), Parkinson’s disease (PD), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), and prion diseases have a certain degree of clinical, pathological, and molecular overlapping. Previous studies revealed that many causative mutations in AD, PD, and FTD/ALS genes could be found in clinical familial and sporadic AD. To further elucidate the missing heritability in early-onset Alzheimer’s disease (EOAD), we genetically characterized a Thai EOAD cohort by Next-Generation Sequencing (NGS) with a high depth of coverage, capturing variants in 50 previously recognized AD and other related disorders’ genes. A novel mutation, APP p.V604M, and the known causative variant, PSEN1 p.E184G, were found in two of the familiar cases. Remarkably, among 61 missense variants were additionally discovered from 21 genes out of 50 genes, six potential mutations including MAPT P513A, LRRK2 p.R1628P, TREM2 p.L211P, and CSF1R (p.P54Q and pL536V) may be considered to be probably/possibly pathogenic and risk factors for other dementia leading to neuronal degeneration. All allele frequencies of the identified missense mutations were compared to 622 control individuals. Our study provides initial evidence that AD and other neurodegenerative diseases may represent shades of the same disease spectrum, and consideration should be given to offer exactly embracing genetic testing to patients diagnosed with EOAD. Our results need to be further confirmed with a larger cohort from this area. MDPI 2019-03-26 /pmc/articles/PMC6471359/ /pubmed/30917570 http://dx.doi.org/10.3390/ijms20061514 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Giau, Vo Van
Senanarong, Vorapun
Bagyinszky, Eva
An, Seong Soo A.
Kim, SangYun
Analysis of 50 Neurodegenerative Genes in Clinically Diagnosed Early-Onset Alzheimer’s Disease
title Analysis of 50 Neurodegenerative Genes in Clinically Diagnosed Early-Onset Alzheimer’s Disease
title_full Analysis of 50 Neurodegenerative Genes in Clinically Diagnosed Early-Onset Alzheimer’s Disease
title_fullStr Analysis of 50 Neurodegenerative Genes in Clinically Diagnosed Early-Onset Alzheimer’s Disease
title_full_unstemmed Analysis of 50 Neurodegenerative Genes in Clinically Diagnosed Early-Onset Alzheimer’s Disease
title_short Analysis of 50 Neurodegenerative Genes in Clinically Diagnosed Early-Onset Alzheimer’s Disease
title_sort analysis of 50 neurodegenerative genes in clinically diagnosed early-onset alzheimer’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471359/
https://www.ncbi.nlm.nih.gov/pubmed/30917570
http://dx.doi.org/10.3390/ijms20061514
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