A novel SOD1 mutation p.V31A identified with a slowly progressive form of amyotrophic lateral sclerosis

作者：Dangoumau Audrey; Verschueren Annie; Hammouche Ellen; Papon Marie Amelie; Blasco Helene; Cherpi Antar Catherine; Pouget Jean; Corcia Philippe; Andres Christian R; Vourc'h Patrick^*

来源：Neurobiology of Aging, 2014, 35(1): 266.e1-266.e4.

DOI：10.1016/j.neurobiolaging.2013.07.012

• ALS
• SOD1
• Mutation

The SOD1 gene encoding the superoxide dismutase 1 (SOD1) protein is mutated in approximately 15% of familial amyotrophic lateral sclerosis (ALS) and 3% of sporadic ALS. We identified a novel mutation in SOD1 in a man who presented at age 49 with lower limb stiffness, and at age 53, a spastic paraparesia with distal muscular atrophy in the lower limbs and fasciculations in the quadriceps. A diagnosis of ALS was established. Eleven years after disease onset his condition continues gradually and slowly to deteriorate. The heterozygous mutation observed in exon 2 resulted in a valine to alanine substitution at position 31 in the beta-barrel domain of the SOD1 protein. Functional analysis in NSC34 cells showed that the overexpression of the mutant form of SOD1(V31A) induced aggregates and decreased cell viability. This mutation is located outside of the regions carrying most of the ALS-related mutations (i.e., the catalytic center, the region of dimerization, and the loops between the beta-strands of the beta-barrel). In conclusion, we identified a novel SOD1 mutation in a patient with slow disease progression and supported the idea that different SOD1 mutations can lead to distinct ALS phenotypes.

• 出版日期2014-1