A Systematic Review of Genotype–Phenotype Correlation across Cohorts Having Causal Mutations of Different Genes in ALS

Amyotrophic lateral sclerosis is a rare and fatal neurodegenerative disease characterised by progressive deterioration of upper and lower motor neurons that eventually culminates in severe muscle atrophy, respiratory failure and death. There is a concerning lack of understanding regarding the mechan...

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Main Authors:	Owen Connolly, Laura Le Gall, Gavin McCluskey, Colette G Donaghy, William J Duddy, Stephanie Duguez
Format:	Article
Language:	English
Published:	MDPI AG 2020-06-01
Series:	Journal of Personalized Medicine
Subjects:	ALS MND ALS variants genotype–phenotype ALS genes
Online Access:	https://www.mdpi.com/2075-4426/10/3/58

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spelling	doaj-ea6734e9763f4c258c1d9e5e3d058f2e2020-11-25T03:47:51ZengMDPI AGJournal of Personalized Medicine2075-44262020-06-0110585810.3390/jpm10030058A Systematic Review of Genotype–Phenotype Correlation across Cohorts Having Causal Mutations of Different Genes in ALSOwen Connolly0Laura Le Gall1Gavin McCluskey2Colette G Donaghy3William J Duddy4Stephanie Duguez5Northern Ireland Center for Stratified/Personalised Medicine, Biomedical Sciences Research Institute, Ulster University, Derry BT47 6SB, Northern Ireland, UKNorthern Ireland Center for Stratified/Personalised Medicine, Biomedical Sciences Research Institute, Ulster University, Derry BT47 6SB, Northern Ireland, UKNorthern Ireland Center for Stratified/Personalised Medicine, Biomedical Sciences Research Institute, Ulster University, Derry BT47 6SB, Northern Ireland, UKDepartment of Neurology, Altnagelvin Hospital, WHSCT, Derry BT47 6SB, Northern Ireland, UKNorthern Ireland Center for Stratified/Personalised Medicine, Biomedical Sciences Research Institute, Ulster University, Derry BT47 6SB, Northern Ireland, UKNorthern Ireland Center for Stratified/Personalised Medicine, Biomedical Sciences Research Institute, Ulster University, Derry BT47 6SB, Northern Ireland, UKAmyotrophic lateral sclerosis is a rare and fatal neurodegenerative disease characterised by progressive deterioration of upper and lower motor neurons that eventually culminates in severe muscle atrophy, respiratory failure and death. There is a concerning lack of understanding regarding the mechanisms that lead to the onset of ALS and as a result there are no reliable biomarkers that aid in the early detection of the disease nor is there an effective treatment. This review first considers the clinical phenotypes associated with ALS, and discusses the broad categorisation of ALS and ALS-mimic diseases into upper and lower motor neuron diseases, before focusing on the genetic aetiology of ALS and considering the potential relationship of mutations of different genes to variations in phenotype. For this purpose, a systematic review is conducted collating data from 107 original published clinical studies on monogenic forms of the disease, surveying the age and site of onset, disease duration and motor neuron involvement. The collected data highlight the complexity of the disease’s genotype–phenotype relationship, and thus the need for a nuanced approach to the development of clinical assays and therapeutics.https://www.mdpi.com/2075-4426/10/3/58ALSMNDALS variantsgenotype–phenotypeALS genes
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Owen Connolly Laura Le Gall Gavin McCluskey Colette G Donaghy William J Duddy Stephanie Duguez
spellingShingle	Owen Connolly Laura Le Gall Gavin McCluskey Colette G Donaghy William J Duddy Stephanie Duguez A Systematic Review of Genotype–Phenotype Correlation across Cohorts Having Causal Mutations of Different Genes in ALS Journal of Personalized Medicine ALS MND ALS variants genotype–phenotype ALS genes
author_facet	Owen Connolly Laura Le Gall Gavin McCluskey Colette G Donaghy William J Duddy Stephanie Duguez
author_sort	Owen Connolly
title	A Systematic Review of Genotype–Phenotype Correlation across Cohorts Having Causal Mutations of Different Genes in ALS
title_short	A Systematic Review of Genotype–Phenotype Correlation across Cohorts Having Causal Mutations of Different Genes in ALS
title_full	A Systematic Review of Genotype–Phenotype Correlation across Cohorts Having Causal Mutations of Different Genes in ALS
title_fullStr	A Systematic Review of Genotype–Phenotype Correlation across Cohorts Having Causal Mutations of Different Genes in ALS
title_full_unstemmed	A Systematic Review of Genotype–Phenotype Correlation across Cohorts Having Causal Mutations of Different Genes in ALS
title_sort	systematic review of genotype–phenotype correlation across cohorts having causal mutations of different genes in als
publisher	MDPI AG
series	Journal of Personalized Medicine
issn	2075-4426
publishDate	2020-06-01
description	Amyotrophic lateral sclerosis is a rare and fatal neurodegenerative disease characterised by progressive deterioration of upper and lower motor neurons that eventually culminates in severe muscle atrophy, respiratory failure and death. There is a concerning lack of understanding regarding the mechanisms that lead to the onset of ALS and as a result there are no reliable biomarkers that aid in the early detection of the disease nor is there an effective treatment. This review first considers the clinical phenotypes associated with ALS, and discusses the broad categorisation of ALS and ALS-mimic diseases into upper and lower motor neuron diseases, before focusing on the genetic aetiology of ALS and considering the potential relationship of mutations of different genes to variations in phenotype. For this purpose, a systematic review is conducted collating data from 107 original published clinical studies on monogenic forms of the disease, surveying the age and site of onset, disease duration and motor neuron involvement. The collected data highlight the complexity of the disease’s genotype–phenotype relationship, and thus the need for a nuanced approach to the development of clinical assays and therapeutics.
topic	ALS MND ALS variants genotype–phenotype ALS genes
url	https://www.mdpi.com/2075-4426/10/3/58
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A Systematic Review of Genotype–Phenotype Correlation across Cohorts Having Causal Mutations of Different Genes in ALS

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