Peters plus syndrome is a new congenital disorder of glycosylation and involves defective O-glycosylation of thrombospondin type 1 repeats
Peters plus syndrome is a new congenital disorder of glycosylation and involves defective O-glycosylation of thrombospondin type 1 repeats
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DOI：
10.1074/jbc.m710251200
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发表时间：
2008-03-21
影响因子：
4.8
通讯作者：
Hofsteenge, Jan
中科院分区：
文献类型：
--
作者：
Hess, Daniel;Keusch, Jeremy J.;Hofsteenge, Jan
彼得斯加综合征是一种常染色体隐性遗传病，其特征是前房缺陷、不成比例的矮小、发育迟缓和唇腭裂。它是由一个被认为是β-1，3-半乳糖基转移酶样基因(B3GALTL)的剪接点突变引起的。最近，我们和其他人发现这个基因编码一个β1，3-葡萄糖基转移酶，参与合成二糖GLC-β1，3-Fuc-O-，它发生在许多生物重要蛋白质的凝血酶反应蛋白1型重复序列上。到目前为止，还没有对Peters Plus综合征中假定的糖基化缺陷进行功能测试。我们建立了一种灵敏的免疫纯化-质谱法，利用多反应监测来分析O-岩藻糖基多糖。用它来比较彼得斯Plus患者和对照杂合子亲属的报告蛋白备解素。在患者的备解素中，我们没有检测到GLC-β1，3-Fuc-O-二糖，我们只在所有四个O-岩藻糖基化位点上发现了Fuc-O-。相反，来自杂合子亲属和健康志愿者的备解素携带GLC-β1，3-Fuc-O-二糖。这些数据确证彼得斯加综合征是一种新的先天性糖基化障碍。
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 beta 1,3-galactosyltransferase-like gene ( B3GALTL). Recently, we and others found this gene to encode a beta 1,3-glucosyltransferase involved in the synthesis of the disaccharide Glc-beta 1,3-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-beta 1,3-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-beta 1,3-Fuc-O-disaccharide. These data firmly establish Peters Plus syndrome as a new congenital disorder of glycosylation.