SRD5A3 Is Required for Converting Polyprenol to Dolichol and Is Mutated in a Congenital Glycosylation Disorder

The document from July 2010 revealed that mutations in the SRD5A3 gene cause a new type of Congenital Disorder of Glycosylation (CDG) by disrupting the conversion of polyprenol to dolichol, which is essential for protein N-glycosylation. The study involved screening 31 patients with CDG-Ix and 7 with clinical overlap for SRD5A3 mutations, using genotyping, linkage analysis, direct sequencing, and mass spectrometry. It was found that SRD5A3 mutations led to a significant increase in the polyprenol to dolichol ratio, indicating a loss of function in the affected patients. The research also demonstrated that the human SRD5A3 gene could rescue glycosylation defects in yeast mutants, suggesting a conserved function across species. The findings highlight the importance of SRD5A3 in the early steps of protein glycosylation and its role in human development and disease.