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

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• 作者：Audrey Dangoumau ; Annie Verschueren ; Ellen Hammouche ; Marie-Am¨¦lie Papon ; H¨¦l¨¨ne Blasco ; Catherine Cherpi-Antar ; Jean Pouget ; Philippe Corcia ; Christian R. Andres ; Patrick Vourc'h
• 关键词：ALS ; SOD1 ; Mutation
• 刊名：Neurobiology of Aging
• 出版年：2014
• 出版时间：January, 2014
• 年：2014
• 卷：35
• 期：1
• 页码：266.e1-266.e4
• 全文大小：722 K

文摘

The m>SOD1m> 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 m>SOD1m> 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 ¦Â-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 ¦Â-strands of the ¦Â-barrel). In conclusion, we identified a novel m>SOD1m> mutation in a patient with slow disease progression and supported the idea that different m>SOD1m> mutations can lead to distinct ALS phenotypes.