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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-06-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/10/3/58 |
| _version_ | 1797563840094797824 |
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| author | Owen Connolly Laura Le Gall Gavin McCluskey Colette G Donaghy William J Duddy Stephanie Duguez |
| author_facet | Owen Connolly Laura Le Gall Gavin McCluskey Colette G Donaghy William J Duddy Stephanie Duguez |
| author_sort | Owen Connolly |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T18:48:53Z |
| format | Article |
| id | doaj.art-ea6734e9763f4c258c1d9e5e3d058f2e |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-10T18:48:53Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-ea6734e9763f4c258c1d9e5e3d058f2e2023-11-20T05:18:51ZengMDPI AGJournal of Personalized Medicine2075-44262020-06-011035810.3390/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, Londonderry BT47 6SB, Northern Ireland, UKNorthern Ireland Center for Stratified/Personalised Medicine, Biomedical Sciences Research Institute, Ulster University, Londonderry BT47 6SB, Northern Ireland, UKNorthern Ireland Center for Stratified/Personalised Medicine, Biomedical Sciences Research Institute, Ulster University, Londonderry BT47 6SB, Northern Ireland, UKDepartment of Neurology, Altnagelvin Hospital, WHSCT, Londonderry BT47 6SB, Northern Ireland, UKNorthern Ireland Center for Stratified/Personalised Medicine, Biomedical Sciences Research Institute, Ulster University, Londonderry BT47 6SB, Northern Ireland, UKNorthern Ireland Center for Stratified/Personalised Medicine, Biomedical Sciences Research Institute, Ulster University, Londonderry 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 |
| 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 |
| title | 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_short | 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 |
| topic | ALS MND ALS variants genotype–phenotype ALS genes |
| url | https://www.mdpi.com/2075-4426/10/3/58 |
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