Open AccessTranslational balancing questioned: Unaltered glycosylation during disulfiram treatment in mannosyl‐oligosaccharide alpha‐1,2‐mannnosidase ‐ congenital disorders of glycosylation (MAN1B1‐CDG)
Author(s) -
Kemme Lisa,
Grüneberg Marianne,
Reunert Janine,
Rust Stephan,
Park Julien,
Westermann Cordula,
Wada Yoshinao,
Schwartz Oliver,
Marquardt Thorsten
Publication year - 2021
Publication title -
jimd reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.412
H-Index - 25
ISSN - 2192-8312
DOI - 10.1002/jmd2.12213
Subject(s) - endoplasmic reticulum , glycosylation , glycoprotein , n linked glycosylation , disulfiram , oligosaccharide , translation (biology) , chemistry , biochemistry , biology , microbiology and biotechnology , messenger rna , gene , glycan
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.