TRAPγ-CDG shows asymmetric glycosylation and an effect on processing of proteins required in higher organisms

J Med Genet. 2021 Mar;58(3):213-216. doi: 10.1136/jmedgenet-2019-106279. Epub 2020 Apr 24.

Abstract

Newly synthesised glycoproteins enter the rough endoplasmic reticulum through a translocation pore. The translocon associated protein (TRAP) complex is located close to the pore. In a patient with a homozygous start codon variant in TRAPγ (SSR3), absence of TRAPγ causes disruption of the TRAP complex, impairs protein translocation into the endoplasmic reticulum and affects transport, for example, into the brush-border membrane. Furthermore, we observed an unbalanced non-occupancy of N-glycosylation sites. The major clinical features are intrauterine growth retardation, facial dysmorphism, congenital diarrhoea, failure to thrive, pulmonary disease and severe psychomotor disability.

Keywords: CDG; TRAP; glycosylation; translocation.

MeSH terms

  • Child
  • Child, Preschool
  • Diarrhea / genetics
  • Diarrhea / pathology
  • Endoplasmic Reticulum, Rough / genetics*
  • Failure to Thrive / genetics
  • Failure to Thrive / pathology
  • Female
  • Fetal Growth Retardation / genetics*
  • Fetal Growth Retardation / pathology
  • Glycoproteins / biosynthesis
  • Glycoproteins / genetics*
  • Glycosylation
  • Humans
  • Infant
  • Infant, Newborn
  • Lung Diseases / genetics
  • Lung Diseases / pathology
  • Male
  • Psychomotor Disorders / genetics
  • Psychomotor Disorders / pathology
  • Tartrate-Resistant Acid Phosphatase / deficiency
  • Tartrate-Resistant Acid Phosphatase / genetics*

Substances

  • Glycoproteins
  • ACP5 protein, human
  • Tartrate-Resistant Acid Phosphatase