SOD1 deficiency: a novel syndrome distinct from amyotrophic lateral sclerosis.
amyotrophic lateral sclerosis
hyperekplexia
oxidative damage
superoxide dismutase
Journal
Brain : a journal of neurology
ISSN: 1460-2156
Titre abrégé: Brain
Pays: England
ID NLM: 0372537
Informations de publication
Date de publication:
01 08 2019
01 08 2019
Historique:
received:
18
01
2019
revised:
22
04
2019
accepted:
28
04
2019
pubmed:
25
7
2019
medline:
27
5
2020
entrez:
24
7
2019
Statut:
ppublish
Résumé
Superoxide dismutase 1 (SOD1) is the principal cytoplasmic superoxide dismutase in humans and plays a major role in redox potential regulation. It catalyses the transformation of the superoxide anion (O2•-) into hydrogen peroxide. Heterozygous variants in SOD1 are a common cause of familial amyotrophic lateral sclerosis. In this study we describe the homozygous truncating variant c.335dupG (p.C112Wfs*11) in SOD1 that leads to total absence of enzyme activity. The resulting phenotype is severe and marked by progressive loss of motor abilities, tetraspasticity with predominance in the lower extremities, mild cerebellar atrophy, and hyperekplexia-like symptoms. Heterozygous carriers have a markedly reduced enzyme activity when compared to wild-type controls but show no overt neurologic phenotype. These results are in contrast with the previously proposed theory that a loss of function is the underlying mechanism in SOD1-related motor neuron disease and should be considered before application of previously proposed SOD1 silencing as a treatment option for amyotrophic lateral sclerosis.
Identifiants
pubmed: 31332433
pii: 5536868
doi: 10.1093/brain/awz182
pmc: PMC6658856
doi:
Substances chimiques
SOD1 protein, human
0
Superoxide Dismutase-1
EC 1.15.1.1
Types de publication
Case Reports
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2230-2237Subventions
Organisme : NCI NIH HHS
ID : R01 CA182804
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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