Glycosylphosphatidylinositol (GPI) anchor deficiency caused by mutations in PIGW is associated with West syndrome and hyperphosphatasia with mental retardation syndrome
Glycosylphosphatidylinositol (GPI) anchor deficiency caused by mutations in PIGW is associated with West syndrome and hyperphosphatasia with mental retardation syndrome
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DOI：
10.1136/jmedgenet-2013-102156
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发表时间：
2014-03-01
影响因子：
4
通讯作者：
Murakami, Yoshiko
中科院分区：
文献类型：
--
作者：
Chiyonobu, Tomohiro;Inoue, Norimitsu;Murakami, Yoshiko
背景糖基磷脂酰肌醇（GPI）是一种糖脂，可将150多种蛋白质锚定在人体细胞表面。至少有26个基因参与GPI锚定蛋白（GPI-AP）的生物合成和重塑。最近，遗传性GPI缺陷（IGDs）被报道，其导致智力残疾，通常伴有癫痫、粗糙的面部特征和多种异常，这些异常的严重程度取决于缺陷的程度和/或受影响基因通路中的步骤。被诊断为韦斯特综合征由于患者表现出严重的发育迟缓，伴有畸形面部特征和高磷酸酶症，这是IGD中常见的特征，因此对患者进行了GPI缺乏症检测。该患者的血液粒细胞表面GPI-AP的表达下降，并被确定为复合杂合子NM_178517：c.211A>C和c.499A>G突变PIGWby targeted sequencing.Conclusion在这里，我们描述了第一个病人与缺乏PIGW，这是参与了在GPI生物合成的早期步骤中添加的酰基链肌醇。因此，在West综合征中应考虑到IGD的存在，流式细胞术检测血细胞是筛查IGD的有效方法。
Background Glycosylphosphatidylinositol (GPI) is a glycolipid that anchors 150 or more kinds of proteins to the human cell surface. There are at least 26 genes involved in the biosynthesis and remodelling of GPI anchored proteins (GPI-APs). Recently, inherited GPI deficiencies (IGDs) were reported which cause intellectual disability often accompanied by epilepsy, coarse facial features and multiple anomalies that vary in severity depending upon the degree of defect and/or step in the pathway of affected gene.Methods and Results A patient born to non-consanguineous parents developed intractable seizures with typical hypsarrhythmic pattern in electroencephalography, and was diagnosed as having West syndrome. Because the patient showed severe developmental delay with dysmorphic facial features and hyperphosphatasia, characteristics often seen in IGDs, the patient was tested for GPI deficiency. The patient had decreased surface expression of GPI-APs on blood granulocytes and was identified to be compound heterozygous for NM_178517:c.211A>C and c.499A>G mutations in PIGW by targeted sequencing.Conclusion Here we describe the first patient with deficiency of PIGW, which is involved in the addition of the acyl-chain to inositol in an early step of GPI biosynthesis. Therefore, IGD should be considered in West syndrome and flow cytometric analysis of blood cells is effective in screening IGD.