Life with too much polyprenol: polyprenol reductase deficiency.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Gründahl, JEH; Guan, Z; Rust, S; Reunert, J; Müller, B; Du Chesne, I; Zerres, K; Rudnik-Schöneborn, S; Ortiz-Brüchle, N; Häusler, MG; Siedlecka, J; Swiezewska, E; Raetz, CRH; Marquardt, T

Published Date

  • April 2012

Published In

Volume / Issue

  • 105 / 4

Start / End Page

  • 642 - 651

PubMed ID

  • 22304929

Pubmed Central ID

  • PMC3428379

Electronic International Standard Serial Number (EISSN)

  • 1096-7206

Digital Object Identifier (DOI)

  • 10.1016/j.ymgme.2011.12.017


  • eng

Conference Location

  • United States