Screening for OST deficiencies in unsolved CDG-I patients

Area of Science:

• Biochemistry
• Genetics
• Molecular Biology

Background:

• Congenital Disorders of Glycosylation (CDG) are inherited defects in glycosylation.
• 14 CDG type I (CDG-I) defects affecting oligosaccharide precursor assembly are known.
• An increasing number of CDG-I patients (CDG-Ix) show protein hypoglycosylation without precursor assembly defects.

Purpose of the Study:

• To investigate if oligosaccharyltransferase (OST) complex deficiency causes hypoglycosylation in CDG-Ix patients.
• To screen OST complex subunits in CDG-Ix patients with normal precursor structures.

Main Methods:

• Screening of OST complex subunits in 27 CDG-Ix patients.
• Analysis of lipid-linked oligosaccharide structure and level.
• Genetic analysis for mutations in OST subunits.

Main Results:

• One patient with unexplained hypoglycosylation was identified.
• The patient had a homozygous missense mutation (c.1121G>A; p.G374D) in the RPN2 subunit of the OST complex.
• The mutation's pathogenic nature requires further validation due to OST defect complexities.

Conclusions:

• A potential link between RPN2 mutations and CDG-Ix is suggested.
• This finding highlights the OST complex as a potential target for diagnosing unexplained CDG.
• Further research is needed to confirm the pathogenicity of the identified RPN2 mutation.