title: Peters Plus syndrome is a new congenital disorder of glycosylation and involves defective Omicron-glycosylation of thrombospondin type 1 repeats.
abstract: 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 beta1,3-galactosyltransferase-like gene (B3GALTL). Recently, we and others found this gene to encode a beta1,3-glucosyltransferase involved in the synthesis of the disaccharide Glc-beta1,3-Fuc-Omicron-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 Omicron-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-beta1,3-Fuc-Omicron-disaccharide, and we only found Fuc-Omicron-at all four Omicron-fucosylation sites. In contrast, properdin from heterozygous relatives and a healthy volunteer carried the Glc-beta1,3-Fuc-Omicron-disaccharide. These data firmly establish Peters Plus syndrome as a new congenital disorder of glycosylation.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel CH-4058, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hess
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Keusch
authors.forename: Saskia A Lesnik
authors.initials: SA
authors.lastname: Oberstein
authors.forename: Raoul C M
authors.initials: RC
authors.lastname: Hennekam
authors.forename: Jan
authors.initials: J
authors.lastname: Hofsteenge
mesh_terms: D000015:Abnormalities, Multiple / Q000201:enzymology* / Q000235:genetics; D020816:Amino Acid Motifs / Q000235:genetics; D002239:Carbohydrate Metabolism, Inborn Errors / Q000201:enzymology* / Q000235:genetics; D004187:Disaccharides / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005700:Galactosyltransferases / Q000235:genetics / Q000378:metabolism*; D005964:Glucosyltransferases; D006031:Glycosylation; D006801:Humans; D008297:Male; D009154:Mutation; D011134:Polysaccharides / Q000096:biosynthesis / Q000235:genetics; D011414:Properdin / Q000235:genetics / Q000378:metabolism; D046188:Protein Modification, Translational / Q000235:genetics*; D022821:RNA Splice Sites / Q000235:genetics*; D013577:Syndrome
chemical_list: D004187:Disaccharides; D011134:Polysaccharides; D022821:RNA Splice Sites; D011414:Properdin; C514116:B3GLCT protein, human; D005700:Galactosyltransferases; D005964:Glucosyltransferases