Ware R E, Rosse W F, Howard T A
Department of Pediatrics, Duke University Medical Center, Durham, NC 27710.
Blood. 1994 May 1;83(9):2418-22.
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematologic disorder with multiple and varied clinical manifestations. The biochemical defect in PNH resides in the incomplete enzymatic assembly of glycosylphosphatidylinositol (GPI) anchors used for surface protein attachment. In all patients tested thus far, the defect is at the level of N-acetylglucosamine attachment to phosphatidylinositol (complementation class A defect). A human cDNA, Piga, that repairs cell lines with the class A defect has been recently cloned, making Piga a candidate gene for PNH. In the current study, using highly purified GPI-deficient granulocytes, we have performed Northern blot and reverse transcriptase polymerase chain reaction (RT-PCR) analysis of Piga in four patients with PNH. In each case, we have identified a mutation in the Piga coding sequence: three frameshift mutations were found, and a single nucleotide substitution (missense) mutation was identified. Our results provide convincing evidence that alterations in the Piga gene are responsible for PNH.
阵发性睡眠性血红蛋白尿（PNH）是一种获得性克隆性血液系统疾病，临床表现多样。PNH的生化缺陷在于用于表面蛋白附着的糖基磷脂酰肌醇（GPI）锚的酶组装不完全。在目前所有检测的患者中，缺陷都发生在N-乙酰葡糖胺与磷脂酰肌醇附着的水平（补体A类缺陷）。最近克隆了一个人类cDNA，即Piga，它能修复具有A类缺陷的细胞系，这使得Piga成为PNH的候选基因。在本研究中，我们使用高度纯化的GPI缺陷粒细胞，对4例PNH患者的Piga进行了Northern印迹和逆转录酶聚合酶链反应（RT-PCR）分析。在每种情况下，我们都在Piga编码序列中发现了一个突变：发现了3个移码突变，并鉴定出一个单核苷酸替代（错义）突变。我们的结果提供了令人信服的证据，表明Piga基因的改变是PNH的病因。
