Title | Biallelic missense variants in COG3 cause a congenital disorder of glycosylation with impairment of retrograde vesicular trafficking. |
Publication Type | Journal Article |
Year of Publication | 2023 |
Authors | Duan, R, Marafi, D, Xia, Z-J, Ng, BG, Maroofian, R, Sumya, FTaher, Saad, AK, Du, H, Fatih, JM, Hunter, JV, Elbendary, HM, Baig, SM, Abdullah, U, Ali, Z, Efthymiou, S, Murphy, D, Mitani, T, Withers, MA, Jhangiani, SN, Coban-Akdemir, Z, Calame, DG, Pehlivan, D, Gibbs, RA, Posey, JE, Houlden, H, Lupashin, VV, Zaki, MS, Freeze, HH, Lupski, JR |
Journal | J Inherit Metab Dis |
Volume | 46 |
Issue | 6 |
Pagination | 1195-1205 |
Date Published | 2023 Nov |
ISSN | 1573-2665 |
Keywords | Adaptor Proteins, Vesicular Transport, Congenital Disorders of Glycosylation, Fibroblasts, Glycosylation, Humans, Phenotype |
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. |
DOI | 10.1002/jimd.12679 |
Alternate Journal | J Inherit Metab Dis |
PubMed ID | 37711075 |
PubMed Central ID | PMC10873070 |
Grant List | R01 GM083144 / GM / NIGMS NIH HHS / United States U54 NS115198 / NS / NINDS NIH HHS / United States T32 GM007526 / GM / NIGMS NIH HHS / United States UM1 HG006542 / HG / NHGRI NIH HHS / United States R35 NS105078 / NS / NINDS NIH HHS / United States K08 HG008986 / HG / NHGRI NIH HHS / United States R01 DK099551 / DK / NIDDK NIH HHS / United States U01 HG011758 / HG / NHGRI NIH HHS / United States |
Biallelic missense variants in COG3 cause a congenital disorder of glycosylation with impairment of retrograde vesicular trafficking.
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