Life with too much polyprenol: polyprenol reductase deficiency

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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Molecular Genetics and Metabolism Elsevier

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Publisher
Elsevier
Copyright
Copyright © 2011 Elsevier Inc.
ISSN
1096-7192
eISSN
1096-7206
DOI
10.1016/j.ymgme.2011.12.017
pmid
22304929
Publisher site
See Article on Publisher Site

Abstract

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.

Journal

Molecular Genetics and MetabolismElsevier

Published: Apr 1, 2012

References

  • CDG nomenclature: time for a change!
    Jaeken, J.; Hennet, T.; Matthijs, G.; Freeze, H.H.
  • Congenital disorders of glycosylation: review of their molecular bases, clinical presentations and specific therapies
    Marquardt, T.; Denecke, J.
  • Cardiomyopathy in congenital disorders of glycosylation
    Gehrmann, J.; Sohlbach, K.; Linnebank, M.; Bohles, H.J.; Buderus, S.; Kehl, H.G.; Vogt, J.; Harms, E.; Marquardt, T.
  • Hypoglycosylation due to dolichol metabolism defects
    Denecke, J.; Kranz, C.
  • Screening and diagnosis of congenital disorders of glycosylation
    Marklova, E.; Albahri, Z.
  • A new autosomal recessive syndrome of ocular colobomas, ichthyosis, brain malformations and endocrine abnormalities in an inbred Emirati family
    Al-Gazali, L.; Hertecant, J.; Algawi, K.; El Teraifi, H.; Dattani, M.
  • Isoprenoids, small GTPases and Alzheimer's disease
    Hooff, G.P.; Wood, W.G.; Muller, W.E.; Eckert, G.P.
  • Translation attenuation by PERK balances ER glycoprotein synthesis with lipid-linked oligosaccharide flux
    Shang, J.; Gao, N.; Kaufman, R.J.; Ron, D.; Harding, H.P.; Lehrman, M.A.

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