Peters Plus Syndrome Is a New Congenital Disorder of Glycosylation and Involves Defective O-Glycosylation of Thrombospondin Type 1 Repeats

Peters Plus syndrome is an autosomal recessive disorder characterized by anterior eye chamber defects, disproportionate short stature, developmental delay, and cleft lip and/or palate. It is caused by splice site mutations in what was thought to be a β1,3-galactosyltransferase-like gene (B3GALTL). R...

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Bibliographic Details
Published in:The Journal of biological chemistry 2008-03, Vol.283 (12), p.7354-7360
Main Authors: Hess, Daniel, Keusch, Jeremy J., Oberstein, Saskia A. Lesnik, Hennekam, Raoul C.M., Hofsteenge, Jan
Format: Article
Language:English
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Summary:Peters Plus syndrome is an autosomal recessive disorder characterized by anterior eye chamber defects, disproportionate short stature, developmental delay, and cleft lip and/or palate. It is caused by splice site mutations in what was thought to be a β1,3-galactosyltransferase-like gene (B3GALTL). Recently, we and others found this gene to encode a β1,3-glucosyltransferase involved in the synthesis of the disaccharide Glc-β1,3-Fuc-O-that occurs on thrombospondin type 1 repeats of many biologically important proteins. No functional tests have been performed to date on the presumed glycosylation defect in Peters Plus syndrome. We have established a sensitive immunopurification-mass spectrometry method, using multiple reaction monitoring, to analyze O-fucosyl glycans. It was used to compare the reporter protein properdin from Peters Plus patients with that from control heterozygous relatives. In properdin from patients, we could not detect the Glc-β1,3-Fuc-O-disaccharide, and we only found Fuc-O-at all four O-fucosylation sites. In contrast, properdin from heterozygous relatives and a healthy volunteer carried the Glc-β1,3-Fuc-O-disaccharide. These data firmly establish Peters Plus syndrome as a new congenital disorder of glycosylation.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M710251200