Savoia A, Ianzano L, Lunardi C, De Sandre G, Carotenuto M, Musto P, Zelante L
Servizio di Genetica Medica, I.R.C.C.S. Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy.
Hum Genet. 1996 Jan;97(1):45-8. doi: 10.1007/BF00218831.
Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired haemolytic disorder caused by the absence of glycosyl phosphatidylinositol (GPI)-anchored surface proteins resulting from a defect in one step of GPI-anchor biosynthesis. Recent analysis has shown that mutations at the PIG-A (phosphatidylinositoglycan-class A) gene are responsible for GPI-anchor deficiency in all PNH patients. In the current study, we describe three new mutations of the PIG-A gene in Italian patients with PNH. The analysis has been performed by RNA/single-strand conformation polymorphism using genomic DNA purified from nucleated peripheral blood cells. An abnormal pattern of migration of polymerase chain reaction amplified fragments containing exons 2 and 5 was observed. Sequencing analysis led to the identification of three mutations: a transversion C-to-A creating a stop codon (Y98X), an A insertion at position 460 (460insA), and a C deletion (1114delC). All the mutations cause a premature termination of the translation of the PIG-A protein.
阵发性夜间血红蛋白尿（PNH）是一种获得性溶血性疾病，由糖基磷脂酰肌醇（GPI）锚定表面蛋白缺失引起，该缺失是由GPI锚生物合成某一步骤的缺陷导致的。最近的分析表明，PIG-A（磷脂酰肌醇聚糖A类）基因突变是所有PNH患者GPI锚缺陷的原因。在本研究中，我们描述了意大利PNH患者中PIG-A基因的三个新突变。分析采用从有核外周血细胞中纯化的基因组DNA，通过RNA/单链构象多态性进行。观察到包含外显子2和5的聚合酶链反应扩增片段的异常迁移模式。测序分析鉴定出三个突变：导致终止密码子的C到A颠换（Y98X）、460位的A插入（460insA）和C缺失（1114delC）。所有突变均导致PIG-A蛋白翻译提前终止。
