SOD1 deficiency: a novel syndrome distinct from amyotrophic lateral sclerosis

Julien H Park; Christiane Elpers; Janine Reunert; Michael L McCormick; Julia Mohr; Saskia Biskup; Oliver Schwartz; Stephan Rust; Marianne Grüneberg; Anja Seelhöfer; Ulrike Schara; Eugen Boltshauser; Douglas R Spitz; Thorsten Marquardt

doi:10.1093/brain/awz182

Back

SOD1 deficiency: a novel syndrome distinct from amyotrophic lateral sclerosis

Journal article

Open access

Peer reviewed

SOD1 deficiency: a novel syndrome distinct from amyotrophic lateral sclerosis

Julien H Park, Christiane Elpers, Janine Reunert, Michael L McCormick, Julia Mohr, Saskia Biskup, Oliver Schwartz, Stephan Rust, Marianne Grüneberg, Anja Seelhöfer, …

Brain (London, England : 1878), Vol.142(8), pp.2230-2237

08/01/2019

DOI: 10.1093/brain/awz182

PMCID: PMC6658856

PMID: 31332433

Files and links (1)

url

https://doi.org/10.1093/brain/awz182View

Published (Version of record) Open Access

Abstract

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.

Amyotrophic Lateral Sclerosis

Child

Child, Preschool

Frameshift Mutation

Heredodegenerative Disorders, Nervous System - genetics

Humans

Male

Pedigree

Superoxide Dismutase-1 - deficiency

Superoxide Dismutase-1 - genetics

Syndrome

Details

Title: Subtitle: SOD1 deficiency: a novel syndrome distinct from amyotrophic lateral sclerosis
Creators: Julien H Park - University of Münster
Christiane Elpers - University of Münster
Janine Reunert - University of Münster
Michael L McCormick - University of Iowa
Julia Mohr - Praxis für Humangenetik Tübingen
Saskia Biskup - Praxis für Humangenetik Tübingen
Oliver Schwartz - University of Münster
Stephan Rust - University of Münster
Marianne Grüneberg - University of Münster
Anja Seelhöfer - University of Münster
Ulrike Schara - Essen University Hospital
Eugen Boltshauser - University Children's Hospital Zurich
Douglas R Spitz - University of Iowa
Thorsten Marquardt - University of Münster
Resource Type: Journal article
Publication Details: Brain (London, England : 1878), Vol.142(8), pp.2230-2237
DOI: 10.1093/brain/awz182
PMID: 31332433
PMCID: PMC6658856
NLM abbreviation: Brain
ISSN: 1460-2156
eISSN: 1460-2156
Grant note: R01 CA182804 / NCI NIH HHS
Language: English
Date published: 08/01/2019
Academic Unit: Pathology; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center
Record Identifier: 9984312971602771

Metrics

17 Record Views

78 Times Cited - Web of Science