An Atypical Presentation of Upper Motor Neuron Predominant Juvenile Amyotrophic Lateral Sclerosis Associated with <i>TARDBP</i> Gene: A Case Report and Review of the Literature
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that can rarely affect young individuals. Juvenile ALS (JALS) is defined for individuals with an onset of the disease before the age of 25. The contribution of genetics to ALS pathology is a field of growing interest. One of the diff...
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MDPI AG
2022-08-01
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| author | Daniel Sánchez-Tejerina Juan Luis Restrepo-Vera Eulalia Rovira-Moreno Marta Codina-Sola Arnau Llauradó Javier Sotoca Maria Salvado Núria Raguer Elena García-Arumí Raúl Juntas-Morales |
| author_facet | Daniel Sánchez-Tejerina Juan Luis Restrepo-Vera Eulalia Rovira-Moreno Marta Codina-Sola Arnau Llauradó Javier Sotoca Maria Salvado Núria Raguer Elena García-Arumí Raúl Juntas-Morales |
| author_sort | Daniel Sánchez-Tejerina |
| collection | DOAJ |
| description | Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that can rarely affect young individuals. Juvenile ALS (JALS) is defined for individuals with an onset of the disease before the age of 25. The contribution of genetics to ALS pathology is a field of growing interest. One of the differences between adult-onset ALS and JALS is their genetic background, with a higher contribution of genetic causes in JALS. We report a patient with JALS and a pathogenic variant in the <i>TARDBP</i> gene (c.1035C > G; p.Asn345Lys), previously reported only in adult-onset ALS, and with an atypical phenotype of marked upper motor neuron predominance. In addition, the proband presented an additional variant in the <i>NEK1</i> gene, c.2961C > G (p.Phe987Leu), which is classified as a variant of unknown significance. Segregation studies showed a paternal origin of the <i>TARDBP</i> variant, while the variant in <i>NEK1</i> was inherited from the mother. We hypothesize that the <i>NEK1</i> variant acts as a disease modifier and suggests the possibility of a functional interaction between both genes in our case. This hypothesis could explain the peculiarities of the phenotype, penetrance, and the age of onset. This report highlights the heterogeneity of the phenotypic presentation of ALS associated with diverse pathogenic genetic variants. |
| first_indexed | 2024-03-09T13:22:56Z |
| format | Article |
| id | doaj.art-f9709e54df794edfa35f3b460eba9d98 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T13:22:56Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-f9709e54df794edfa35f3b460eba9d982023-11-30T21:28:21ZengMDPI AGGenes2073-44252022-08-01138148310.3390/genes13081483An Atypical Presentation of Upper Motor Neuron Predominant Juvenile Amyotrophic Lateral Sclerosis Associated with <i>TARDBP</i> Gene: A Case Report and Review of the LiteratureDaniel Sánchez-Tejerina0Juan Luis Restrepo-Vera1Eulalia Rovira-Moreno2Marta Codina-Sola3Arnau Llauradó4Javier Sotoca5Maria Salvado6Núria Raguer7Elena García-Arumí8Raúl Juntas-Morales9Neuromuscular Diseases Unit, European Reference Network on Rare Neuromuscular Diseases (ERN EURO-NMD), Department of Neurology, Vall d’Hebron University Hospital, Passeig de la Vall d’Hebron, 119, 08035 Barcelona, SpainNeuromuscular Diseases Unit, European Reference Network on Rare Neuromuscular Diseases (ERN EURO-NMD), Department of Neurology, Vall d’Hebron University Hospital, Passeig de la Vall d’Hebron, 119, 08035 Barcelona, SpainDepartment of Clinical and Molecular Genetics, Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, 08035 Barcelona, SpainDepartment of Clinical and Molecular Genetics, Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, 08035 Barcelona, SpainNeuromuscular Diseases Unit, European Reference Network on Rare Neuromuscular Diseases (ERN EURO-NMD), Department of Neurology, Vall d’Hebron University Hospital, Passeig de la Vall d’Hebron, 119, 08035 Barcelona, SpainNeuromuscular Diseases Unit, European Reference Network on Rare Neuromuscular Diseases (ERN EURO-NMD), Department of Neurology, Vall d’Hebron University Hospital, Passeig de la Vall d’Hebron, 119, 08035 Barcelona, SpainNeuromuscular Diseases Unit, European Reference Network on Rare Neuromuscular Diseases (ERN EURO-NMD), Department of Neurology, Vall d’Hebron University Hospital, Passeig de la Vall d’Hebron, 119, 08035 Barcelona, SpainDepartment of Clinical Neurophysiology, Vall d’Hebron University Hospital, Passeig de la Vall d’Hebron, 119, 08035 Barcelona, SpainDepartment of Clinical and Molecular Genetics, Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, 08035 Barcelona, SpainNeuromuscular Diseases Unit, European Reference Network on Rare Neuromuscular Diseases (ERN EURO-NMD), Department of Neurology, Vall d’Hebron University Hospital, Passeig de la Vall d’Hebron, 119, 08035 Barcelona, SpainAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that can rarely affect young individuals. Juvenile ALS (JALS) is defined for individuals with an onset of the disease before the age of 25. The contribution of genetics to ALS pathology is a field of growing interest. One of the differences between adult-onset ALS and JALS is their genetic background, with a higher contribution of genetic causes in JALS. We report a patient with JALS and a pathogenic variant in the <i>TARDBP</i> gene (c.1035C > G; p.Asn345Lys), previously reported only in adult-onset ALS, and with an atypical phenotype of marked upper motor neuron predominance. In addition, the proband presented an additional variant in the <i>NEK1</i> gene, c.2961C > G (p.Phe987Leu), which is classified as a variant of unknown significance. Segregation studies showed a paternal origin of the <i>TARDBP</i> variant, while the variant in <i>NEK1</i> was inherited from the mother. We hypothesize that the <i>NEK1</i> variant acts as a disease modifier and suggests the possibility of a functional interaction between both genes in our case. This hypothesis could explain the peculiarities of the phenotype, penetrance, and the age of onset. This report highlights the heterogeneity of the phenotypic presentation of ALS associated with diverse pathogenic genetic variants.https://www.mdpi.com/2073-4425/13/8/1483<i>TARDBP</i>TDP-43juvenile amyotrophic lateral sclerosisupper motor neuron predominant disorder |
| spellingShingle | Daniel Sánchez-Tejerina Juan Luis Restrepo-Vera Eulalia Rovira-Moreno Marta Codina-Sola Arnau Llauradó Javier Sotoca Maria Salvado Núria Raguer Elena García-Arumí Raúl Juntas-Morales An Atypical Presentation of Upper Motor Neuron Predominant Juvenile Amyotrophic Lateral Sclerosis Associated with <i>TARDBP</i> Gene: A Case Report and Review of the Literature Genes <i>TARDBP</i> TDP-43 juvenile amyotrophic lateral sclerosis upper motor neuron predominant disorder |
| title | An Atypical Presentation of Upper Motor Neuron Predominant Juvenile Amyotrophic Lateral Sclerosis Associated with <i>TARDBP</i> Gene: A Case Report and Review of the Literature |
| title_full | An Atypical Presentation of Upper Motor Neuron Predominant Juvenile Amyotrophic Lateral Sclerosis Associated with <i>TARDBP</i> Gene: A Case Report and Review of the Literature |
| title_fullStr | An Atypical Presentation of Upper Motor Neuron Predominant Juvenile Amyotrophic Lateral Sclerosis Associated with <i>TARDBP</i> Gene: A Case Report and Review of the Literature |
| title_full_unstemmed | An Atypical Presentation of Upper Motor Neuron Predominant Juvenile Amyotrophic Lateral Sclerosis Associated with <i>TARDBP</i> Gene: A Case Report and Review of the Literature |
| title_short | An Atypical Presentation of Upper Motor Neuron Predominant Juvenile Amyotrophic Lateral Sclerosis Associated with <i>TARDBP</i> Gene: A Case Report and Review of the Literature |
| title_sort | atypical presentation of upper motor neuron predominant juvenile amyotrophic lateral sclerosis associated with i tardbp i gene a case report and review of the literature |
| topic | <i>TARDBP</i> TDP-43 juvenile amyotrophic lateral sclerosis upper motor neuron predominant disorder |
| url | https://www.mdpi.com/2073-4425/13/8/1483 |
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