Identification of a novel homozygous synthesis of cytochrome c oxidase 2 variant in siblings with early-onset axonal Charcot-Marie-Tooth disease.
Authors
Hentschel, Andreas
Rademacher, Nina
Sickmann, Albert
Stüve, Burkhard
Horvath, Rita
Gross, Claudia
Förster, Fabian
Abicht, Angela
Publication Date
2022-04Journal Title
Hum Mutat
ISSN
1059-7794
Publisher
Hindawi Limited
Language
en
Type
Other
This Version
AO
VoR
Metadata
Show full item recordCitation
Gangfuß, A., Hentschel, A., Rademacher, N., Sickmann, A., Stüve, B., Horvath, R., Gross, C., et al. (2022). Identification of a novel homozygous synthesis of cytochrome c oxidase 2 variant in siblings with early-onset axonal Charcot-Marie-Tooth disease.. [Other]. https://doi.org/10.1002/humu.24338
Description
Funder: European Regional Development Fund (ERDF); Id: http://dx.doi.org/10.13039/501100008530
Funder: Regierenden Bürgermeister von Berlin ‐ Senatskanzlei Wissenschaft und Forschung
Funder: Bundesministerium für Bildung und Forschung; Id: http://dx.doi.org/10.13039/501100002347
Funder: Ministerium für Kultur und Wissenschaft des Landes Nordrhein‐Westfalen; Id: http://dx.doi.org/10.13039/501100014690
Abstract
The synthesis of cytochrome c oxidase 2 (SCO2 ) gene encodes for a mitochondrial located metallochaperone essential for the synthesis of the cytochrome c oxidase (COX) subunit 2. Recessive mutations in SCO2 have been reported in several cases with fatal infantile cardioencephalomyopathy with COX deficiency and in only four cases with axonal neuropathy. Here, we identified a homozygous pathogenic variant (c.361G > C; p.[Gly121Arg]) in SCO2 in two brothers with isolated axonal motor neuropathy. To address pathogenicity of the amino acid substitution, biochemical studies were performed and revealed increased level of the mutant SCO2 -protein and dysregulation of COX subunits in leukocytes and moreover unraveled decrease of proteins involved in the manifestation of neuropathies. Hence, our combined data strengthen the concept of SCO2 being causative for a very rare form of axonal neuropathy, expand its molecular genetic spectrum and provide first biochemical insights into the underlying pathophysiology.
Keywords
BRIEF REPORT, axonal neuropathy, Charcot‐Marie‐Tooth disease, synthesis of cytochrome c oxidase 2 (SCO2), white blood cell proteomics
Sponsorship
Leibniz‐Research‐Cluster (031A360E)
Identifiers
humu24338
External DOI: https://doi.org/10.1002/humu.24338
This record's DOI: https://doi.org/10.17863/CAM.81493
Rights
Licence:
http://creativecommons.org/licenses/by-nc-nd/4.0/
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