6 research outputs found
Life with too much polyprenol: polyprenol reductase deficiency
Congenital disorders of glycosylation (CDG) are caused by a dysfunction of glycosylation, an essential step in
the manufacturing process of glycoproteins. This paper focuses on a 6-year-old patient with a new type of
CDG-I caused by a defect of the steroid 5α reductase type 3 gene (SRD5A3). The clinical features were psychomotor
retardation, pathological nystagmus, slight muscular hypotonia and microcephaly. SRD5A3 was recently
identified encoding the polyprenol reductase, an enzyme catalyzing the final step of the biosynthesis
of dolichol, which is required for the assembly of the glycans needed for N-glycosylation.
Although an early homozygous stop-codon (c.57G>A [W19X]) with no functional protein was found in the
patient, about 70% of transferrin (Tf) was correctly glycosylated. Quantification of dolichol and unreduced
polyprenol in the patient's fibroblasts demonstrated a high polyprenol/dolichol ratio with normal amounts
of dolichol, indicating that high polyprenol levels might compete with dolichol for the initiation of
N-glycan assembly but without supporting normal glycosylation and that there must be an alternative
pathway for dolichol biosynthesis