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Life with too much polyprenol: polyprenol reductase deficiency

Gründahl, J and Guan, Z and Rust, S and Reunert, J and Müller, B and Du Chesne, I and Zerres, K and Rudnik-Schöneborn, S and Ortiz-Brüchle, N and Häusler, M and Siedlecka, J and Swiezewska, Ewa and Raetz, C and Marquardt, T (2012) Life with too much polyprenol: polyprenol reductase deficiency. Molecular Genetics and Metabolism, 105 . pp. 642-651.

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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.

Item Type:Article
Subjects:Q Science > QH Natural history > QH301 Biology
Divisions:Department of Lipid Biochemistry
ID Code:353
Deposited By: Ewa Swiezewska
Deposited On:01 Oct 2012 11:11
Last Modified:01 Oct 2012 11:11

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