Characterizing SOD1 mutations in Spain : The impact of genotype, age and sex in the natural history of the disease
Vázquez-Costa, Juan F. (Universitat de València)
Borrego-Hernández, Daniel (Hospital 12 de Octubre (Madrid))
Paradas, Carmen (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Gómez-Caravaca, María Teresa (Hospital Universitario Reina Sofía (Còrdova, Espanya))
Rojas-Garcia, Ricardo (Institut d'Investigació Biomèdica Sant Pau)
Varona, Luis (Hospital Universitario de Basurto (Bilbao, Biscaia))
Povedano, Mónica (Institut d'Investigació Biomèdica de Bellvitge)
García-Sobrino, Tania (Complejo Hospitalario Universitario de Santiago de Compostela)
Jericó-Pascual, Ivonne (Hospital Universitario de Navarra (HUN) and IdisNA)
Gutiérrez, Antonio (Complejo Hospitalario Universitario Insular Materno Infantil (Las Palmas de Gran Canaria))
Riancho, Javier (Hospital Sierrallana-IDIVAL)
Turon-Sans, Janina (Institut d'Investigació Biomèdica Sant Pau)
Assialioui, Abdelilah (Institut d'Investigació Biomèdica de Bellvitge)
Pérez-Tur, Jordi (Instituto de Biomedicina de Valencia (IBV-CSIC))
Sevilla, Teresa (Universitat de València)
Esteban Pérez, Jordi (Hospital 12 de Octubre (Madrid))
García-Redondo, Alberto (Hospital 12 de Octubre (Madrid))
Andrés López, Alberto
Calabria, M. Dolores
Díaz-Marín, Carmen
Fages Caravaca, Eva
Galán Dávila, Lucía
García Martínez, Alberto
Gimenez-Muñoz, Álvaro
Guerrero Sola, Antonio
Mascías Cadavid, Javier
Mora Pardina, Jesús S.
Muñoz Blanco, José Luis
Juntas-Morales, Raúl
Morgado, Yolanda
Pardo, Julio
Valladares, Amador
Vilar-Ventura, Rosa María
Universitat Autònoma de Barcelona

Date:	2023
Abstract:	The aim of this study was to describe the frequency and distribution of SOD1 mutations in Spain, and to explore factors contributing to their phenotype and prognosis. Seventeen centres shared data on amyotrophic lateral sclerosis (ALS) patients carrying pathogenic or likely pathogenic SOD1 variants. Multivariable models were used to explore prognostic modifiers. In 144 patients (from 88 families), 29 mutations (26 missense, 2 deletion/insertion and 1 frameshift) were found in all five exons of SOD1, including seven novel mutations. A total of 2. 6% of ALS patients (including 17. 7% familial and 1. 3% sporadic) were estimated to carry SOD1 mutations. The frequency of this mutation varied considerably among regions, due to founder events. The most frequent mutation was p. Gly38Arg (n = 58), followed by p. Glu22Gly (n = 11), p. Asn140His (n = 10), and the novel p. Leu120Val (n = 10). Most mutations were characterized by a protracted course, and some of them by atypical phenotypes. Older age of onset was independently associated with faster disease progression (exp[Estimate] = 1. 03 [0. 01, 0. 05], p = 0. 001) and poorer survival (hazard ratio 1. 05 [1. 01, 1. 08], p = 0. 007), regardless of the underlying mutation. Female sex was independently associated with faster disease progression (exp[Estimate] = 2. 1 [1. 23, 3. 65], p = 0. 012) in patients carrying the p. Gly38Arg mutation, resulting in shorter survival compared with male carriers (236 vs. 301 months). These data may help to evaluate the efficacy of SOD1 targeted treatments, and to expand the number of patients that might benefit from these treatments.
Grants:	Instituto de Salud Carlos III PI21/00737 Instituto de Salud Carlos III PI19/01178 Instituto de Salud Carlos III PI19/01543
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Amyotrophic lateral sclerosis ; SOD1 ; Motor neuron disease ; Mutation ; Prevalence ; Prognosis
Published in:	European Journal of Neurology, Vol. 30 Núm. 4 (april 2023) , p. 861-871, ISSN 1468-1331

DOI: 10.1111/ene.15661
PMID: 36484631

11 p, 2.0 MB

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Articles > Research articles
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