DEFICIENCY OF THE GPI ANCHOR CAUSED BY A SOMATIC MUTATION OF THE PIG-A GENE IN PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA
DEFICIENCY OF THE GPI ANCHOR CAUSED BY A SOMATIC MUTATION OF THE PIG-A GENE IN PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA
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DOI：
10.1016/0092-8674(93)90250-t
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发表时间：
1993-05-21
期刊：
影响因子：
64.5
通讯作者：
KINOSHITA, T
中科院分区：
文献类型：
--
作者：
TAKEDA, J;MIYATA, T;KINOSHITA, T
阵发性睡眠性血红蛋白尿症是一种获得性血液病，其特征是血细胞群体异常，糖基磷脂酰肌醇(GPI)锚的生物合成不足。GPI锚定的补体抑制物表面表达不足会导致补体介导的溶血。在这里，我们报道了参与GPI锚生物合成早期步骤的PIG-A是导致阵发性睡眠性血红蛋白尿的基因。受影响的粒细胞和B淋巴细胞具有与PIG-A相同的体细胞突变，表明它们的克隆性起源于多潜能的造血干细胞。我们将PIG-A定位到X染色体，这解释了体细胞突变的隐性表型的表达，以及到目前为止所有患者中多个生物合成步骤中的同一个步骤受到影响的事实。
Paroxysmal nocturnal hemoglobinuria is an acquired hematopoietic disease characterized by abnormal blood cell populations in which the biosynthesis of the glycosylphosphatidylinositol (GPI) anchor is deficient. Deficiency of surface expressions of GPI-anchored complement inhibitors leads to complement-mediated hemolysis. Here we report that PIG-A, which participates in the early step of GPI anchor biosynthesis, is the gene responsible for paroxysmal nocturnal hemoglobinuria. Affected granulocytes and B lymphocytes had the same somatic mutation of PIG-A, indicating their clonal origin from a multipotential hematopoietic stem cell. We localized PIG-A to the X chromosome, which accounts for expression of the recessive phenotype of the somatic mutation and the fact that the same one of the multiple biosynthetic steps is affected in all patients so far characterized.