TY - JOUR
T1 - Biallelic missense variants in COG3 cause a congenital disorder of glycosylation with impairment of retrograde vesicular trafficking
AU - Duan, Ruizhi
AU - Marafi, Dana
AU - Xia, Zhi Jie
AU - Ng, Bobby G.
AU - Maroofian, Reza
AU - Sumya, Farhana Taher
AU - Saad, Ahmed K.
AU - Du, Haowei
AU - Fatih, Jawid M.
AU - Hunter, Jill V.
AU - Elbendary, Hasnaa M.
AU - Baig, Shahid M.
AU - Abdullah, Uzma
AU - Ali, Zafar
AU - Efthymiou, Stephanie
AU - Murphy, David
AU - Mitani, Tadahiro
AU - Withers, Marjorie A.
AU - Jhangiani, Shalini N.
AU - Coban-Akdemir, Zeynep
AU - Calame, Daniel G.
AU - Pehlivan, Davut
AU - Gibbs, Richard A.
AU - Posey, Jennifer E.
AU - Houlden, Henry
AU - Lupashin, Vladimir V.
AU - Zaki, Maha S.
AU - Freeze, Hudson H.
AU - Lupski, James R.
N1 - Publisher Copyright:
© 2023 SSIEM.
PY - 2023/11
Y1 - 2023/11
N2 - 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.
AB - 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.
KW - AOH/ROH analysis
KW - congenital disorders of glycosylation
KW - conserved oligomeric Golgi complex
KW - family-based genomic analysis
KW - retrograde vesicular transport
UR - http://www.scopus.com/inward/record.url?scp=85173433622&partnerID=8YFLogxK
U2 - 10.1002/jimd.12679
DO - 10.1002/jimd.12679
M3 - Article
C2 - 37711075
AN - SCOPUS:85173433622
SN - 0141-8955
VL - 46
SP - 1195
EP - 1205
JO - Journal of Inherited Metabolic Disease
JF - Journal of Inherited Metabolic Disease
IS - 6
ER -