학술논문
Characterizing SOD1 mutations in Spain: The impact of genotype, age and sex in the natural history of the disease.
Document Type
Article
Author
Vázquez‐Costa, Juan F.; Borrego‐Hernández, Daniel; Paradas, Carmen; Gómez‐Caravaca, María Teresa; Rojas‐Garcia, Ricardo; Varona, Luis; Povedano, Mónica; García‐Sobrino, Tania; Jericó Pascual, Ivonne; Gutiérrez, Antonio; Riancho, Javier; Turon‐Sans, Janina; Assialioui, Abdelilah; Pérez‐Tur, Jordi; Sevilla, Teresa; Esteban Pérez, Jesús; García‐Redondo, Alberto; López, Alberto Andrés; Calabria, M. Dolores; Díaz‐Marín, Carmen
Source
Subject
*AMYOTROPHIC lateral sclerosis
*GENETIC mutation
*SERVER farms (Computer network management)
*GENOTYPES
*MOTOR neuron diseases
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Language
ISSN
1351-5101
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. [ABSTRACT FROM AUTHOR]