Kinoshita T
Department of Immunoregulation, Osaka University.
Rinsho Ketsueki. 1993 May;34(5):529-36.
Paroxysmal nocturnal hemoglobinuria (PNH) is a hemolytic anemia caused by complement-mediated hemolysis. Blood cells from patients with PNH contain abnormal cells that lack complement regulatory proteins, DAF and CD59, both of which protect host cells from action of complement. DAF and CD59 are GPI-anchored and on the abnormal blood cells other GPI-anchored proteins are also deficient. A fundamental abnormality of PNH appeared to be deficient biosynthesis of the GPI-anchor at an early step. We cloned a cDNA of a gene termed PIG-A (for Phosphatidyl Inositol Glycan-class A) that encodes a 484 amino acid putative ER membrane protein which functions at that step and hence a responsible gene for PNH. Analysis of PIG-A transcripts in the abnormal cells from patients with PNH demonstrated various types of abnormalities such as decreased level of the transcript, splicing abnormality and mutations in the coding region. Thus, PNH is caused by a clonal expansion of abnormal blood cells derived from a hematopoietic stem cell bearing a somatic mutation occurred in PIG-A gene.
阵发性夜间血红蛋白尿（PNH）是一种由补体介导的溶血引起的溶血性贫血。PNH患者的血细胞含有缺乏补体调节蛋白DAF和CD59的异常细胞，这两种蛋白均可保护宿主细胞免受补体作用。DAF和CD59通过糖基磷脂酰肌醇（GPI）锚定，在异常血细胞上其他GPI锚定蛋白也存在缺陷。PNH的一个基本异常似乎是早期GPI锚定生物合成不足。我们克隆了一个名为PIG-A（磷脂酰肌醇聚糖A类）的基因的cDNA，该基因编码一种484个氨基酸的假定内质网（ER）膜蛋白，在该步骤发挥作用，因此是PNH的致病基因。对PNH患者异常细胞中PIG-A转录本的分析显示出各种类型的异常，如转录本水平降低、剪接异常和编码区突变。因此，PNH是由携带PIG-A基因体细胞突变的造血干细胞衍生的异常血细胞的克隆性扩增引起的。
