Journalartikel
Autorenliste: Gangfuss, Andrea; Hentschel, Andreas; Rademacher, Nina; Sickmann, Albert; Stueve, Burkhard; Horvath, Rita; Gross, Claudia; Kohlschmidt, Nicolai; Foerster, Fabian; Abicht, Angela; Schaenzer, Anne; Schara-Schmidt, Ulrike; Roos, Andreas; Della Marina, Adela
Jahr der Veröffentlichung: 2022
Seiten: 477-486
Zeitschrift: Human Mutation: Variation, Informatics and Disease
Bandnummer: 43
Heftnummer: 4
ISSN: 1059-7794
eISSN: 1098-1004
Open Access Status: Gold
DOI Link: https://doi.org/10.1002/humu.24338
Verlag: Wiley
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.
Zitierstile
Harvard-Zitierstil: Gangfuss, A., Hentschel, A., Rademacher, N., Sickmann, A., Stueve, B., Horvath, R., 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, Human Mutation: Variation, Informatics and Disease, 43(4), pp. 477-486. https://doi.org/10.1002/humu.24338
APA-Zitierstil: Gangfuss, A., Hentschel, A., Rademacher, N., Sickmann, A., Stueve, B., Horvath, R., Gross, C., Kohlschmidt, N., Foerster, F., Abicht, A., Schaenzer, A., Schara-Schmidt, U., Roos, A., & Della Marina, A. (2022). Identification of a novel homozygous synthesis of cytochrome c oxidase 2 variant in siblings with early-onset axonal Charcot-Marie-Tooth disease. Human Mutation: Variation, Informatics and Disease. 43(4), 477-486. https://doi.org/10.1002/humu.24338
Schlagwörter
axonal neuropathy; CARDIOENCEPHALOMYOPATHY; Cardiomyopathy; Charcot-Marie-Tooth disease; COPPER-BINDING PROTEIN; NEUROPATHY; SCO2 MUTATION; synthesis of cytochrome c oxidase 2 (SCO2); white blood cell proteomics
