Original articleA new mutation in COG7 extends the spectrum of COG subunit deficiencies
Introduction
The Conserved Oligomeric Golgi (COG) complex is a hetero-octameric protein complex, located in the cytoplasmic part of the Golgi membrane and consisting of 8 subunits organized into two lobes: lobe A (Cog1-4) and lobe B (Cog5-8). Six patients from 4 families with a defect in N- and O-glycosylation and the same mutation in COG7, c.169 + 4 A > C, have been described [2], [3], [4], [8]. The North African origin of these patients suggested a common ancestral mutation and they all presented with a similar phenotype [9]. In a large group of unsolved CDG patients with a type 2 pattern on isoelectric focusing (IEF) of serum transferrin, we looked for defects in the subunits of the COG complex and found a patient with a novel mutation in COG7.
Section snippets
Methods
IEF of serum transferrin and apolipoprotein C-III (apoC-III) were performed using the methods described by respectively Jaeken et al. [1] and Wopereis et al. [7]. Permethylated N-glycans of serum transferrin were analysed by matrix assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS) in negative and positive ion mode [6]. Western blot analysis of the different COG subunits and molecular analysis of the different COG genes was performed as described [2]. Finally, Brefeldin A
Patient description
This boy was born as the first child to consanguineous healthy Moroccan parents by caesarean section because of breech presentation. Birthweight was 3050 g, length 48 cm and head circumference 34 cm. Symptomatology started from the age of 1 month with diarrhoea and severe dehydratation, hepatomegaly, cholestasis, anaemia, thrombocytopenia, and mild proteinuria. MRI of the brain showed cerebral atrophy and a hypodensity in the periventricular white matter. Psychomotor development was delayed and
Discussion
Previously, six patients from four different families were reported with the same mutation, c.169+4A > C, in COG7[2], [3], [4], [8]. Here we present a new patient with a different intronic mutation in COG7, c.170-7A > G, and his brother with most probably the same disease. This mutation results in the activation of a cryptic splice donor site and insertion of 6 basepairs. The resulting protein is predicted to contain two additional amino acids, alanine and threonine.
Major differences in
Acknowledgements
This research was funded by grants from the European Commission (Fifth Framework Programme, contract LSHM-CT.2005–512131 to EUROGLYCANET; http://www.euroglycanet.org) and from the Research Foundation (FWO) Flanders (contract G.0173.04). Renate Zeevaert is research assistant of the FWO. We thank Wim Annaert, Ellen Reynders and Liesbeth Keldermans for helpful collaboration and technical support.
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