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Novel Genetic Signatures Associated With Sporadic Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a complex polygenetic neurodegenerative disorder. Establishing a diagnosis for ALS is a challenging and lengthy process. By the time a diagnosis is made, the lifespan prognosis is only about two to 5 years. Genetic testing can be critical in assessing a patient...

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Autores principales: Logan, Robert, Dubel-Haag, Juleah, Schcolnicov, Nicolas, Miller, Sean J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8986983/
https://www.ncbi.nlm.nih.gov/pubmed/35401706
http://dx.doi.org/10.3389/fgene.2022.851496
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author Logan, Robert
Dubel-Haag, Juleah
Schcolnicov, Nicolas
Miller, Sean J.
author_facet Logan, Robert
Dubel-Haag, Juleah
Schcolnicov, Nicolas
Miller, Sean J.
author_sort Logan, Robert
collection PubMed
description Amyotrophic Lateral Sclerosis (ALS) is a complex polygenetic neurodegenerative disorder. Establishing a diagnosis for ALS is a challenging and lengthy process. By the time a diagnosis is made, the lifespan prognosis is only about two to 5 years. Genetic testing can be critical in assessing a patient’s risk for ALS, provided they have one of the known familial genes. However, the vast majority of ALS cases are sporadic and have no known associated genetic signatures. Our analysis of the whole genome sequencing data from ALS patients and healthy controls from the Answer ALS Consortium has uncovered twenty-three novel mutations in twenty-two protein-coding genes associated with sporadic ALS cases. The results show the majority of patients with the sporadic form of ALS have at least one or more mutation(s) in the 22 genes we have identified with probabilities of developing ALS ranging from 25–99%, depending on the number of mutations a patient has among the identified genes. Moreover, we have identified a subset of the ALS cohort that has >17 mutations in the 22 identified. In this case, a patient with this mutation profile has a 99% chance of developing ALS and could be classified as being at high risk for the disease. These genetic biomarkers can be used as an early ALS disease diagnostic tool with a rapid and non-invasive technique.
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spelling pubmed-89869832022-04-08 Novel Genetic Signatures Associated With Sporadic Amyotrophic Lateral Sclerosis Logan, Robert Dubel-Haag, Juleah Schcolnicov, Nicolas Miller, Sean J. Front Genet Genetics Amyotrophic Lateral Sclerosis (ALS) is a complex polygenetic neurodegenerative disorder. Establishing a diagnosis for ALS is a challenging and lengthy process. By the time a diagnosis is made, the lifespan prognosis is only about two to 5 years. Genetic testing can be critical in assessing a patient’s risk for ALS, provided they have one of the known familial genes. However, the vast majority of ALS cases are sporadic and have no known associated genetic signatures. Our analysis of the whole genome sequencing data from ALS patients and healthy controls from the Answer ALS Consortium has uncovered twenty-three novel mutations in twenty-two protein-coding genes associated with sporadic ALS cases. The results show the majority of patients with the sporadic form of ALS have at least one or more mutation(s) in the 22 genes we have identified with probabilities of developing ALS ranging from 25–99%, depending on the number of mutations a patient has among the identified genes. Moreover, we have identified a subset of the ALS cohort that has >17 mutations in the 22 identified. In this case, a patient with this mutation profile has a 99% chance of developing ALS and could be classified as being at high risk for the disease. These genetic biomarkers can be used as an early ALS disease diagnostic tool with a rapid and non-invasive technique. Frontiers Media S.A. 2022-03-24 /pmc/articles/PMC8986983/ /pubmed/35401706 http://dx.doi.org/10.3389/fgene.2022.851496 Text en Copyright © 2022 Logan, Dubel-Haag, Schcolnicov and Miller. 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 Genetics
Logan, Robert
Dubel-Haag, Juleah
Schcolnicov, Nicolas
Miller, Sean J.
Novel Genetic Signatures Associated With Sporadic Amyotrophic Lateral Sclerosis
title Novel Genetic Signatures Associated With Sporadic Amyotrophic Lateral Sclerosis
title_full Novel Genetic Signatures Associated With Sporadic Amyotrophic Lateral Sclerosis
title_fullStr Novel Genetic Signatures Associated With Sporadic Amyotrophic Lateral Sclerosis
title_full_unstemmed Novel Genetic Signatures Associated With Sporadic Amyotrophic Lateral Sclerosis
title_short Novel Genetic Signatures Associated With Sporadic Amyotrophic Lateral Sclerosis
title_sort novel genetic signatures associated with sporadic amyotrophic lateral sclerosis
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8986983/
https://www.ncbi.nlm.nih.gov/pubmed/35401706
http://dx.doi.org/10.3389/fgene.2022.851496
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