Translational balancing questioned: Unaltered glycosylation during disulfiram treatment in mannosyl-oligosaccharide alpha-1,2-mannnosidase-congenital disorders of glycosylation (MAN1B1-CDG).

Autor: Kemme L; University Children's Hospital Münster Muenster Germany., Grüneberg M; University Children's Hospital Münster Muenster Germany., Reunert J; University Children's Hospital Münster Muenster Germany., Rust S; University Children's Hospital Münster Muenster Germany., Park J; University Children's Hospital Münster Muenster Germany.; Department of Clinical Sciences, Neurosciences Umeå University Umeå Sweden., Westermann C; Gerhard-Domagk-Institute of Pathology University Hospital Muenster Muenster Germany., Wada Y; Osaka Medical Center and Research Institute for Maternal and Child Health Osaka Japan., Schwartz O; University Children's Hospital Münster Muenster Germany., Marquardt T; University Children's Hospital Münster Muenster Germany.
Jazyk: angličtina
Zdroj: JIMD reports [JIMD Rep] 2021 Mar 20; Vol. 60 (1), pp. 42-55. Date of Electronic Publication: 2021 Mar 20 (Print Publication: 2021).
DOI: 10.1002/jmd2.12213
Abstrakt: MAN1B1-CDG is a multisystem disorder caused by mutations in MAN1B1 , encoding the endoplasmic reticulum mannosyl-oligosaccharide alpha-1,2-mannnosidase. A defect leads to dysfunction within the degradation of misfolded glycoproteins. We present two additional patients with MAN1B1-CDG and a resulting defect in endoplasmic reticulum-associated protein degradation. One patient (P2) is carrying the previously undescribed p.E663K mutation. A therapeutic trial in patient 1 (P1) using disulfiram with the rationale to generate an attenuation of translation and thus a balanced, restored ER glycoprotein synthesis failed. No improvement of the transferrin glycosylation profile was seen.
Competing Interests: The authors declare no conflict of interests.
(© 2021 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM.)
Databáze: MEDLINE
Externí odkaz: