Familial ALS is associated with mutations in all exons of SOD1: a novel mutation in exon 3 (Gly72Ser)

Mutations of the SOD1 gene, which encodes the enzyme copper/zinc superoxide dismutase, are associated with familial amyotrophic lateral sclerosis (ALS). SOD1 consists of five exons, and over 50 different mutations have been described involving exons 1,2,4 and 5. The absence of mutations in exon 3 ha...

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Bibliographic Details
Published in:Journal of the neurological sciences 1997-12, Vol.153 (1), p.46-49
Main Authors: Orrell, R.W, Marklund, S.L, deBelleroche, J.S
Format: Article
Language:English
Subjects:
Amyotrophic lateral sclerosis
Amyotrophic Lateral Sclerosis - enzymology
Amyotrophic Lateral Sclerosis - genetics
Biological and medical sciences
Chromosomes, Human, Pair 21
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Exons - genetics
Familial
Genetics
Humans
Male
Medical sciences
Middle Aged
Mutation
Neurology
Point Mutation - genetics
Point Mutation - physiology
Progressive muscular atrophy
SOD1
Superoxide Dismutase - genetics
Superoxide Dismutase - metabolism
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Summary:Mutations of the SOD1 gene, which encodes the enzyme copper/zinc superoxide dismutase, are associated with familial amyotrophic lateral sclerosis (ALS). SOD1 consists of five exons, and over 50 different mutations have been described involving exons 1,2,4 and 5. The absence of mutations in exon 3 has been attributed to a critical function of this exon, its integrity being necessary for the toxic effect of mutant SOD1, and it has been suggested that such mutations may be lethal rather than leading to adult onset disease. We identified the heterozygote mutation Gly72Ser (exon 3) in a family with two individuals affected by ALS. SOD enzyme activity was reduced by 45% when measured in erythrocytes indicating reduced enzyme activity, or reduced stability of the mutant protein. These findings indicate that exon 3 is not a privileged region from mutation; that all five exons should be investigated when seeking SOD1 mutations in human disease; and may help in a better understanding of the pathogenicity of these mutations in ALS.
ISSN:0022-510X
1878-5883
DOI:10.1016/S0022-510X(97)00181-0