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Characterizing SOD1 mutations in Spain. The impact of genotype, age, and sex in the natural history of the disease.

Fecha de publicación: Fecha Ahead of Print:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • Borrego-Hernandez, Daniel
  • Gómez-Caravaca MT
  • Rojas-Garcia, Ricardo
  • Varona, Luis
  • Povedano, Monica
  • Garcia-Sobrino, Tania
  • Jerico Pascual, Ivonne
  • Riancho, Javier
  • Turon-Sans, Janina
  • Assialioui, Abdelilah
  • Esteban Perez, Jesus
  • Garcia-Redondo, Alberto
  • ALSGESCO

Grupos

Abstract

INTRODUCTION: The aim of this study is to describe the frequency and distribution of SOD1 mutations in Spain, and to explore those factors contributing to their phenotype and prognosis. METHODS: 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. RESULTS: In 144 patients (from 88 families), 29 mutations (26 missense, 2 deletion/insertion and 1 frameshift) were found in all 5 exons of SOD1, including 7 novel mutations. 2.6% of ALS patients (including 17.7% familial and 1.3% sporadic) were estimated to carry SOD1 mutations. Its frequency varied considerably between 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 (HR = 1.05 [1.01, 1.08], p = 0.007), regardless of the underlying mutation. Female sex was independently associated to 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). CONCLUSIONS: 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.

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Datos de la publicación

ISSN/ISSNe:
1351-5101, 1468-1331

EUROPEAN JOURNAL OF NEUROLOGY  WILEY

Tipo:
Article
Páginas:
861-871
PubMed:
36484631
Enlace a otro recurso:
www.scopus.com
Factor de Impacto:
1,662 SCImago ℠
Cuartil:
Q1 SCImago ℠

Citas Recibidas en Web of Science: 8

Citas Recibidas en Scopus: 6

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Keywords

  • Amyotrophic lateral sclerosis; SOD1; motor neuron disease; mutation; prevalence; prognosis

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