Buscar

Estamos realizando la búsqueda. Por favor, espere...

 Detalle_Publicacion

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

Abstract: Background and purpose: 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. 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 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). 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.

 Autoría: Vázquez-Costa J.F., Borrego-Hernández D., Paradas C., Gómez-Caravaca M.T., Rojas-Garcia R., Varona L., Povedano M., García-Sobrino T., Jericó Pascual I., Gutiérrez A., Riancho J., Turon-Sans J., Assialioui A., Pérez-Tur J., Sevilla T., Esteban Pérez J., García-Redondo A., López A.A., Calabria M.D., Díaz-Marín C., Caravaca E.F., Dávila L.G., Martínez A.G., Gimenez-Muñoz Á., Sola A.G., Cadavid J.M., Mora Pardina J.S., Blanco J.L.M., Juntas-Mo

 Fuente: European Journal of Neurology, 2023, 30, 861-871

Editorial: Wiley

 Año de publicación: 2023

Nº de páginas: 11

Tipo de publicación: Artículo de Revista

 DOI: 10.1111/ene.15661

ISSN: 1351-5101,1468-1331

Url de la publicación: https://doi.org/10.1111/ene.15661

Autores/as

VÁZQUEZ-COSTA, JUAN F.

BORREGO-HERNÁNDEZ, DANIEL

PARADAS, CARMEN

GÓMEZ-CARAVACA, MARÍA TERESA

ROJAS-GARCÍA, RICARDO

VARONA, LUIS

POVEDANO, MÓNICA

GARCÍA-SOBRINO, TANIA

JERICÓ PASCUAL, IVONNE

GUTIÉRREZ, ANTONIO

TURON-SANS, JANINA

ASSIALIOUI, ABDELILAH

PÉREZ-TUR, JORDI

SEVILLA, TERESA

ESTEBAN PÉREZ, JESÚS

GARCÍA-REDONDO, ALBERTO