UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Biallelic missense variants in COG3 cause a congenital disorder of glycosylation with impairment of retrograde vesicular trafficking

Duan, R; Marafi, D; Xia, ZJ; Ng, BG; Maroofian, R; Sumya, FT; Saad, AK; ... Lupski, JR; + view all (2023) Biallelic missense variants in COG3 cause a congenital disorder of glycosylation with impairment of retrograde vesicular trafficking. Journal of Inherited Metabolic Disease 10.1002/jimd.12679. (In press).

[thumbnail of Efthymiou_COG3 manuscript_JIMD_R1_Tracked Changes_V4.pdf] Text
Efthymiou_COG3 manuscript_JIMD_R1_Tracked Changes_V4.pdf
Access restricted to UCL open access staff until 6 October 2024.

Download (262kB)

Abstract

Biallelic variants in genes for seven out of eight subunits of the conserved oligomeric Golgi complex (COG) are known to cause recessive congenital disorders of glycosylation (CDG) with variable clinical manifestations. COG3 encodes a constituent subunit of the COG complex that has not been associated with disease traits in humans. Herein, we report two COG3 homozygous missense variants in four individuals from two unrelated consanguineous families that co-segregated with COG3–CDG presentations. Clinical phenotypes of affected individuals include global developmental delay, severe intellectual disability, microcephaly, epilepsy, facial dysmorphism, and variable neurological findings. Biochemical analysis of serum transferrin from one family showed the loss of a single sialic acid. Western blotting on patient-derived fibroblasts revealed reduced COG3 and COG4. Further experiments showed delayed retrograde vesicular recycling in patient cells. This report adds to the knowledge of the COG–CDG network by providing collective evidence for a COG3–CDG rare disease trait and implicating a likely pathology of the disorder as the perturbation of Golgi trafficking.

Type: Article
Title: Biallelic missense variants in COG3 cause a congenital disorder of glycosylation with impairment of retrograde vesicular trafficking
Location: United States
DOI: 10.1002/jimd.12679
Publisher version: https://doi.org/10.1002/jimd.12679
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: AOH/ROH analysis, congenital disorders of glycosylation, conserved oligomeric Golgi complex, family-based genomic analysis, retrograde vesicular transport
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10179975
Downloads since deposit
1Download
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item