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An Atypical Presentation of Upper Motor Neuron Predominant Juvenile Amyotrophic Lateral Sclerosis Associated with TARDBP 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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Autores principales: Sánchez-Tejerina, Daniel, Restrepo-Vera, Juan Luis, Rovira-Moreno, Eulalia, Codina-Sola, Marta, Llauradó, Arnau, Sotoca, Javier, Salvado, Maria, Raguer, Núria, García-Arumí, Elena, Juntas-Morales, Raúl
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9407925/
https://www.ncbi.nlm.nih.gov/pubmed/36011394
http://dx.doi.org/10.3390/genes13081483
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author Sánchez-Tejerina, Daniel
Restrepo-Vera, Juan Luis
Rovira-Moreno, Eulalia
Codina-Sola, Marta
Llauradó, Arnau
Sotoca, Javier
Salvado, Maria
Raguer, Núria
García-Arumí, Elena
Juntas-Morales, Raúl
author_facet Sánchez-Tejerina, Daniel
Restrepo-Vera, Juan Luis
Rovira-Moreno, Eulalia
Codina-Sola, Marta
Llauradó, Arnau
Sotoca, Javier
Salvado, Maria
Raguer, Núria
García-Arumí, Elena
Juntas-Morales, Raúl
author_sort Sánchez-Tejerina, Daniel
collection PubMed
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 TARDBP 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 NEK1 gene, c.2961C > G (p.Phe987Leu), which is classified as a variant of unknown significance. Segregation studies showed a paternal origin of the TARDBP variant, while the variant in NEK1 was inherited from the mother. We hypothesize that the NEK1 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.
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spelling pubmed-94079252022-08-26 An Atypical Presentation of Upper Motor Neuron Predominant Juvenile Amyotrophic Lateral Sclerosis Associated with TARDBP Gene: A Case Report and Review of the Literature Sánchez-Tejerina, Daniel Restrepo-Vera, Juan Luis Rovira-Moreno, Eulalia Codina-Sola, Marta Llauradó, Arnau Sotoca, Javier Salvado, Maria Raguer, Núria García-Arumí, Elena Juntas-Morales, Raúl Genes (Basel) Case Report 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 TARDBP 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 NEK1 gene, c.2961C > G (p.Phe987Leu), which is classified as a variant of unknown significance. Segregation studies showed a paternal origin of the TARDBP variant, while the variant in NEK1 was inherited from the mother. We hypothesize that the NEK1 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. MDPI 2022-08-19 /pmc/articles/PMC9407925/ /pubmed/36011394 http://dx.doi.org/10.3390/genes13081483 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Sánchez-Tejerina, Daniel
Restrepo-Vera, Juan Luis
Rovira-Moreno, Eulalia
Codina-Sola, Marta
Llauradó, Arnau
Sotoca, Javier
Salvado, Maria
Raguer, Núria
García-Arumí, Elena
Juntas-Morales, Raúl
An Atypical Presentation of Upper Motor Neuron Predominant Juvenile Amyotrophic Lateral Sclerosis Associated with TARDBP Gene: A Case Report and Review of the Literature
title An Atypical Presentation of Upper Motor Neuron Predominant Juvenile Amyotrophic Lateral Sclerosis Associated with TARDBP 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 TARDBP 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 TARDBP 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 TARDBP 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 TARDBP Gene: A Case Report and Review of the Literature
title_sort atypical presentation of upper motor neuron predominant juvenile amyotrophic lateral sclerosis associated with tardbp gene: a case report and review of the literature
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9407925/
https://www.ncbi.nlm.nih.gov/pubmed/36011394
http://dx.doi.org/10.3390/genes13081483
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