Novel Pathogenic Variants Leading to Sporadic Amyotrophic Lateral Sclerosis in Greek Patients
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive disease that affects motor neurons, leading to paralysis and death usually 3–5 years after the onset of symptoms. The investigation of both sporadic and familial ALS highlighted four main genes that contribute to the pathogenesis of the di...
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MDPI AG
2024-02-01
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| Online Access: | https://www.mdpi.com/2073-4425/15/3/309 |
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| author | Ouliana Ivantsik Anne John Kyriaki Kydonopoulou Konstantinos Mitropoulos Spyridon Gerou Bassam R. Ali George P. Patrinos |
| author_facet | Ouliana Ivantsik Anne John Kyriaki Kydonopoulou Konstantinos Mitropoulos Spyridon Gerou Bassam R. Ali George P. Patrinos |
| author_sort | Ouliana Ivantsik |
| collection | DOAJ |
| description | Amyotrophic lateral sclerosis (ALS) is a rapidly progressive disease that affects motor neurons, leading to paralysis and death usually 3–5 years after the onset of symptoms. The investigation of both sporadic and familial ALS highlighted four main genes that contribute to the pathogenesis of the disease: <i>SOD1</i>, <i>FUS</i>, <i>TARDBP</i> and <i>C9orf72</i>. This study aims to provide a comprehensive investigation of genetic variants found in <i>SOD1</i>, <i>FUS</i> and <i>TARDBP</i> genes in Greek sporadic ALS (sALS) cases. Our sequencing analysis of the coding regions of the abovementioned genes that include the majority of the variants that lead to ALS in 32 sALS patients and 3 healthy relatives revealed 6 variants in <i>SOD1</i>, 19 variants in <i>FUS</i> and 37 variants in <i>TARDBP</i>, of which the <i>SOD1</i> p.D90A and the <i>FUS</i> c.*356G>A (rs886051940) variants have been previously associated with ALS, while two novel nonsense pathogenic variants were also identified, namely FUS p.R241* and TDP-43 p.Y214*. Our study contributes to the worldwide effort toward clarifying the genetic basis of sALS to better understand the disease’s molecular pathology. |
| first_indexed | 2024-04-24T18:14:58Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-04-24T18:14:58Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-abfcac454b2b465aba7a7dd3aa96f6fd2024-03-27T13:43:02ZengMDPI AGGenes2073-44252024-02-0115330910.3390/genes15030309Novel Pathogenic Variants Leading to Sporadic Amyotrophic Lateral Sclerosis in Greek PatientsOuliana Ivantsik0Anne John1Kyriaki Kydonopoulou2Konstantinos Mitropoulos3Spyridon Gerou4Bassam R. Ali5George P. Patrinos6Laboratory of Pharmacogenomics and Individualized Therapy, Division of Pharmacology and Biosciences, Department of Pharmacy, School of Health Sciences, University of Patras, 26504 Rion, GreeceDepartment of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain P.O. Box 15551, United Arab EmiratesANALYSI Biomedical Laboratories S.A., 54623 Thessaloniki, GreeceDepartment of Histology and Embryology, School of Medicine, National and Kapodistrian University of Athens, 10679 Athens, GreeceANALYSI Biomedical Laboratories S.A., 54623 Thessaloniki, GreeceDepartment of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain P.O. Box 15551, United Arab EmiratesLaboratory of Pharmacogenomics and Individualized Therapy, Division of Pharmacology and Biosciences, Department of Pharmacy, School of Health Sciences, University of Patras, 26504 Rion, GreeceAmyotrophic lateral sclerosis (ALS) is a rapidly progressive disease that affects motor neurons, leading to paralysis and death usually 3–5 years after the onset of symptoms. The investigation of both sporadic and familial ALS highlighted four main genes that contribute to the pathogenesis of the disease: <i>SOD1</i>, <i>FUS</i>, <i>TARDBP</i> and <i>C9orf72</i>. This study aims to provide a comprehensive investigation of genetic variants found in <i>SOD1</i>, <i>FUS</i> and <i>TARDBP</i> genes in Greek sporadic ALS (sALS) cases. Our sequencing analysis of the coding regions of the abovementioned genes that include the majority of the variants that lead to ALS in 32 sALS patients and 3 healthy relatives revealed 6 variants in <i>SOD1</i>, 19 variants in <i>FUS</i> and 37 variants in <i>TARDBP</i>, of which the <i>SOD1</i> p.D90A and the <i>FUS</i> c.*356G>A (rs886051940) variants have been previously associated with ALS, while two novel nonsense pathogenic variants were also identified, namely FUS p.R241* and TDP-43 p.Y214*. Our study contributes to the worldwide effort toward clarifying the genetic basis of sALS to better understand the disease’s molecular pathology.https://www.mdpi.com/2073-4425/15/3/309amyotrophic lateral sclerosissporadic ALSgenetics<i>SOD1</i><i>FUS</i><i>TARDBP</i> |
| spellingShingle | Ouliana Ivantsik Anne John Kyriaki Kydonopoulou Konstantinos Mitropoulos Spyridon Gerou Bassam R. Ali George P. Patrinos Novel Pathogenic Variants Leading to Sporadic Amyotrophic Lateral Sclerosis in Greek Patients Genes amyotrophic lateral sclerosis sporadic ALS genetics <i>SOD1</i> <i>FUS</i> <i>TARDBP</i> |
| title | Novel Pathogenic Variants Leading to Sporadic Amyotrophic Lateral Sclerosis in Greek Patients |
| title_full | Novel Pathogenic Variants Leading to Sporadic Amyotrophic Lateral Sclerosis in Greek Patients |
| title_fullStr | Novel Pathogenic Variants Leading to Sporadic Amyotrophic Lateral Sclerosis in Greek Patients |
| title_full_unstemmed | Novel Pathogenic Variants Leading to Sporadic Amyotrophic Lateral Sclerosis in Greek Patients |
| title_short | Novel Pathogenic Variants Leading to Sporadic Amyotrophic Lateral Sclerosis in Greek Patients |
| title_sort | novel pathogenic variants leading to sporadic amyotrophic lateral sclerosis in greek patients |
| topic | amyotrophic lateral sclerosis sporadic ALS genetics <i>SOD1</i> <i>FUS</i> <i>TARDBP</i> |
| url | https://www.mdpi.com/2073-4425/15/3/309 |
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