Details

Autor(en) / Beteiligte

• Hess, Daniel
• Keusch, Jeremy J.
• Oberstein, Saskia A. Lesnik
• Hennekam, Raoul C.M.
• Hofsteenge, Jan

Titel

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

Ist Teil von

• The Journal of biological chemistry, 2008-03, Vol.283 (12), p.7354-7360

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2008

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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.