Individual Oligogenic Background in p.D91A-<i>SOD1</i> Amyotrophic Lateral Sclerosis Patients
The p.D91A is one of the most common ALS-causing <i>SOD1</i> mutations and is known to be either recessive or dominant. The homozygous phenotype is characterized by prolonged survival and slow progression of disease, whereas the affected heterozygous phenotypes can vary. To date, no gene...
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MDPI AG
2021-11-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/12/12/1843 |
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| author | Giulia Gentile Benedetta Perrone Giovanna Morello Isabella Laura Simone Sebastiano Andò Sebastiano Cavallaro Francesca Luisa Conforti |
| author_facet | Giulia Gentile Benedetta Perrone Giovanna Morello Isabella Laura Simone Sebastiano Andò Sebastiano Cavallaro Francesca Luisa Conforti |
| author_sort | Giulia Gentile |
| collection | DOAJ |
| description | The p.D91A is one of the most common ALS-causing <i>SOD1</i> mutations and is known to be either recessive or dominant. The homozygous phenotype is characterized by prolonged survival and slow progression of disease, whereas the affected heterozygous phenotypes can vary. To date, no genetic protective factors located close to <i>SOD1</i> have been associated with the mild progressive homozygous phenotype. Using Next Generation Sequencing (NGS), we characterized a small cohort of sporadic and familial p.D91A-<i>SOD1</i> heterozygous (<i>n</i> = 2) or homozygous (<i>n</i> = 5) ALS patients, to reveal any additional contributing variant in 39 ALS-related genes. We detected unique sets of non-synonymous variants, four of which were of uncertain significance and several in untranslated regions of ALS-related genes. Our results supported an individual oligogenic background underlying both sporadic and familial p.D91A cases irrespective of their p.D91A mutant alleles. We suggest that a comprehensive genomic view of p.D91A-<i>SOD1</i> ALS patients may be useful in identifying emerging variants and improving disease diagnosis as well as guiding precision medicine. |
| first_indexed | 2024-03-10T04:03:50Z |
| format | Article |
| id | doaj.art-f3309cac3c974ca69e40821d64527b96 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T04:03:50Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
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| spelling | doaj.art-f3309cac3c974ca69e40821d64527b962023-11-23T08:29:17ZengMDPI AGGenes2073-44252021-11-011212184310.3390/genes12121843Individual Oligogenic Background in p.D91A-<i>SOD1</i> Amyotrophic Lateral Sclerosis PatientsGiulia Gentile0Benedetta Perrone1Giovanna Morello2Isabella Laura Simone3Sebastiano Andò4Sebastiano Cavallaro5Francesca Luisa Conforti6Institute for Biomedical Research and Innovation, Department of Biomedical Sciences, National Research Council (CNR), 95126 Catania, ItalyMedical Genetics Laboratory, Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, 87036 Rende, ItalyInstitute for Biomedical Research and Innovation, Department of Biomedical Sciences, National Research Council (CNR), 95126 Catania, ItalyNeurology Unit, Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari “Aldo Moro”, 70121 Bari, ItalyMedical Genetics Laboratory, Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, 87036 Rende, ItalyInstitute for Biomedical Research and Innovation, Department of Biomedical Sciences, National Research Council (CNR), 95126 Catania, ItalyMedical Genetics Laboratory, Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, 87036 Rende, ItalyThe p.D91A is one of the most common ALS-causing <i>SOD1</i> mutations and is known to be either recessive or dominant. The homozygous phenotype is characterized by prolonged survival and slow progression of disease, whereas the affected heterozygous phenotypes can vary. To date, no genetic protective factors located close to <i>SOD1</i> have been associated with the mild progressive homozygous phenotype. Using Next Generation Sequencing (NGS), we characterized a small cohort of sporadic and familial p.D91A-<i>SOD1</i> heterozygous (<i>n</i> = 2) or homozygous (<i>n</i> = 5) ALS patients, to reveal any additional contributing variant in 39 ALS-related genes. We detected unique sets of non-synonymous variants, four of which were of uncertain significance and several in untranslated regions of ALS-related genes. Our results supported an individual oligogenic background underlying both sporadic and familial p.D91A cases irrespective of their p.D91A mutant alleles. We suggest that a comprehensive genomic view of p.D91A-<i>SOD1</i> ALS patients may be useful in identifying emerging variants and improving disease diagnosis as well as guiding precision medicine.https://www.mdpi.com/2073-4425/12/12/1843p.D91A-<i>SOD1</i>zygosityNGS targeted-gene panelindividual oligogenic background |
| spellingShingle | Giulia Gentile Benedetta Perrone Giovanna Morello Isabella Laura Simone Sebastiano Andò Sebastiano Cavallaro Francesca Luisa Conforti Individual Oligogenic Background in p.D91A-<i>SOD1</i> Amyotrophic Lateral Sclerosis Patients Genes p.D91A-<i>SOD1</i> zygosity NGS targeted-gene panel individual oligogenic background |
| title | Individual Oligogenic Background in p.D91A-<i>SOD1</i> Amyotrophic Lateral Sclerosis Patients |
| title_full | Individual Oligogenic Background in p.D91A-<i>SOD1</i> Amyotrophic Lateral Sclerosis Patients |
| title_fullStr | Individual Oligogenic Background in p.D91A-<i>SOD1</i> Amyotrophic Lateral Sclerosis Patients |
| title_full_unstemmed | Individual Oligogenic Background in p.D91A-<i>SOD1</i> Amyotrophic Lateral Sclerosis Patients |
| title_short | Individual Oligogenic Background in p.D91A-<i>SOD1</i> Amyotrophic Lateral Sclerosis Patients |
| title_sort | individual oligogenic background in p d91a i sod1 i amyotrophic lateral sclerosis patients |
| topic | p.D91A-<i>SOD1</i> zygosity NGS targeted-gene panel individual oligogenic background |
| url | https://www.mdpi.com/2073-4425/12/12/1843 |
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