A new inborn error of glycosylation due to a Cog8 deficiency reveals a critical role for the Cog1-Cog8 interaction in COG complex formation

F. Foulquier; D. Ungar; E. Reynders; R. Zeevaert; P. Mills; M.T. García-Silva; P. Briones; B. Winchester; W. Morelle; M. Krieger; W. Annaert; G. Matthijs

doi:10.1093/hmg/ddl476

A new inborn error of glycosylation due to a Cog8 deficiency reveals a critical role for the Cog1-Cog8 interaction in COG complex formation

F. Foulquier, D. Ungar, E. Reynders, R. Zeevaert, P. Mills, M.T. García-Silva, P. Briones, B. Winchester, W. Morelle, M. Krieger, W. Annaert, G. Matthijs

Biology

Research output: Contribution to journal › Article › peer-review

Abstract

The hetero-octameric conserved oligomeric Golgi (COG) complex is essential for the structure/function of the Golgi apparatus through regulation of membrane trafficking. Here, we describe a patient with a mild form of a congenital disorder of glycosylation type II (CDG-II), which is caused by a homozygous nonsense mutation in the hCOG8 gene. This leads to a premature stop codon resulting in a truncated Cog8 subunit lacking the 76 C-terminal amino acids. Mass spectrometric analysis of the N- and O-glycan structures identified a mild sialylation deficiency. We showed that the molecular basis of this defect in N- and O-glycosylation is caused by the disruption of the Cog1–Cog8 interaction due to truncation. As a result, Cog1 deficiency accompanies the Cog8 deficiency, preventing assembly of the intact, stable complex and resulting in the appearance of smaller subcomplexes. Moreover, levels of ß1,4-galactosytransferase were significantly reduced. The defects in O-glycosylation could be fully restored by transfecting the patient's fibroblasts with full-length Cog8. The Cog8 defect described here represents a novel type of CDG-II, which we propose to name as CDG-IIh or CDG caused by Cog8 deficiency (CDG-II/Cog8).

Original language	English
Pages (from-to)	717-730
Number of pages	13
Journal	Human Molecular Genetics
Volume	16
Issue number	7
DOIs	https://doi.org/10.1093/hmg/ddl476
Publication status	Published - Jan 2007

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10.1093/hmg/ddl476

http://dx.doi.org/10.1093/hmg/ddl476

Cite this

Foulquier, F., Ungar, D., Reynders, E., Zeevaert, R., Mills, P., García-Silva, M. T., Briones, P., Winchester, B., Morelle, W., Krieger, M., Annaert, W., & Matthijs, G. (2007). A new inborn error of glycosylation due to a Cog8 deficiency reveals a critical role for the Cog1-Cog8 interaction in COG complex formation. Human Molecular Genetics, 16(7), 717-730. https://doi.org/10.1093/hmg/ddl476

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title = "A new inborn error of glycosylation due to a Cog8 deficiency reveals a critical role for the Cog1-Cog8 interaction in COG complex formation",

abstract = "The hetero-octameric conserved oligomeric Golgi (COG) complex is essential for the structure/function of the Golgi apparatus through regulation of membrane trafficking. Here, we describe a patient with a mild form of a congenital disorder of glycosylation type II (CDG-II), which is caused by a homozygous nonsense mutation in the hCOG8 gene. This leads to a premature stop codon resulting in a truncated Cog8 subunit lacking the 76 C-terminal amino acids. Mass spectrometric analysis of the N- and O-glycan structures identified a mild sialylation deficiency. We showed that the molecular basis of this defect in N- and O-glycosylation is caused by the disruption of the Cog1–Cog8 interaction due to truncation. As a result, Cog1 deficiency accompanies the Cog8 deficiency, preventing assembly of the intact, stable complex and resulting in the appearance of smaller subcomplexes. Moreover, levels of {\ss}1,4-galactosytransferase were significantly reduced. The defects in O-glycosylation could be fully restored by transfecting the patient's fibroblasts with full-length Cog8. The Cog8 defect described here represents a novel type of CDG-II, which we propose to name as CDG-IIh or CDG caused by Cog8 deficiency (CDG-II/Cog8).",

author = "F. Foulquier and D. Ungar and E. Reynders and R. Zeevaert and P. Mills and M.T. Garc{\'i}a-Silva and P. Briones and B. Winchester and W. Morelle and M. Krieger and W. Annaert and G. Matthijs",

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doi = "10.1093/hmg/ddl476",

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Foulquier, F, Ungar, D, Reynders, E, Zeevaert, R, Mills, P, García-Silva, MT, Briones, P, Winchester, B, Morelle, W, Krieger, M, Annaert, W & Matthijs, G 2007, 'A new inborn error of glycosylation due to a Cog8 deficiency reveals a critical role for the Cog1-Cog8 interaction in COG complex formation', Human Molecular Genetics, vol. 16, no. 7, pp. 717-730. https://doi.org/10.1093/hmg/ddl476

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T1 - A new inborn error of glycosylation due to a Cog8 deficiency reveals a critical role for the Cog1-Cog8 interaction in COG complex formation

AU - Foulquier, F.

AU - Ungar, D.

AU - Reynders, E.

AU - Zeevaert, R.

AU - Mills, P.

AU - García-Silva, M.T.

AU - Briones, P.

AU - Winchester, B.

AU - Morelle, W.

AU - Krieger, M.

AU - Annaert, W.

AU - Matthijs, G.

PY - 2007/1

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N2 - The hetero-octameric conserved oligomeric Golgi (COG) complex is essential for the structure/function of the Golgi apparatus through regulation of membrane trafficking. Here, we describe a patient with a mild form of a congenital disorder of glycosylation type II (CDG-II), which is caused by a homozygous nonsense mutation in the hCOG8 gene. This leads to a premature stop codon resulting in a truncated Cog8 subunit lacking the 76 C-terminal amino acids. Mass spectrometric analysis of the N- and O-glycan structures identified a mild sialylation deficiency. We showed that the molecular basis of this defect in N- and O-glycosylation is caused by the disruption of the Cog1–Cog8 interaction due to truncation. As a result, Cog1 deficiency accompanies the Cog8 deficiency, preventing assembly of the intact, stable complex and resulting in the appearance of smaller subcomplexes. Moreover, levels of ß1,4-galactosytransferase were significantly reduced. The defects in O-glycosylation could be fully restored by transfecting the patient's fibroblasts with full-length Cog8. The Cog8 defect described here represents a novel type of CDG-II, which we propose to name as CDG-IIh or CDG caused by Cog8 deficiency (CDG-II/Cog8).

AB - The hetero-octameric conserved oligomeric Golgi (COG) complex is essential for the structure/function of the Golgi apparatus through regulation of membrane trafficking. Here, we describe a patient with a mild form of a congenital disorder of glycosylation type II (CDG-II), which is caused by a homozygous nonsense mutation in the hCOG8 gene. This leads to a premature stop codon resulting in a truncated Cog8 subunit lacking the 76 C-terminal amino acids. Mass spectrometric analysis of the N- and O-glycan structures identified a mild sialylation deficiency. We showed that the molecular basis of this defect in N- and O-glycosylation is caused by the disruption of the Cog1–Cog8 interaction due to truncation. As a result, Cog1 deficiency accompanies the Cog8 deficiency, preventing assembly of the intact, stable complex and resulting in the appearance of smaller subcomplexes. Moreover, levels of ß1,4-galactosytransferase were significantly reduced. The defects in O-glycosylation could be fully restored by transfecting the patient's fibroblasts with full-length Cog8. The Cog8 defect described here represents a novel type of CDG-II, which we propose to name as CDG-IIh or CDG caused by Cog8 deficiency (CDG-II/Cog8).

U2 - 10.1093/hmg/ddl476

DO - 10.1093/hmg/ddl476

M3 - Article

SN - 0964-6906

VL - 16

SP - 717

EP - 730

JO - Human Molecular Genetics

JF - Human Molecular Genetics

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