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 (Hospital Universitari Vall d'Hebron)
Restrepo, Juan Luis (Hospital Universitari Vall d'Hebron)
Rovira-Moreno, Eulalia (Hospital Universitari Vall d'Hebron)
Codina Solà, Marta (Hospital Universitari Vall d'Hebron)
Llaurado, Arnau (Hospital Universitari Vall d'Hebron)
Sotoca Fernández, Javier (Hospital Universitari Vall d'Hebron)
Salvado, Maria (Hospital Universitari Vall d'Hebron)
Raguer, Nuria (Hospital Universitari Vall d'Hebron)
Garcia-Arumi, Elena (Hospital Universitari Vall d'Hebron)
Juntas Morales, Raúl (Hospital Universitari Vall d'Hebron)
Universitat Autònoma de Barcelona

Data:	2022
Resum:	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.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Juvenile amyotrophic lateral sclerosis ; TARDBP ; TDP-43 ; Upper motor neuron predominant disorder
Publicat a:	Genes, Vol. 13 Núm. 8 (august 2022) , p. 1483, ISSN 2073-4425

DOI: 10.3390/genes13081483
PMID: 36011394

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