Lin L I, Liu C H, Chen Y C, Shen M C, Wang C H, Huang Y L, Lin J K
Graduate Institute of Biochemistry, National Taiwan University, Taipei.
Br J Haematol. 1997 May;97(2):286-92. doi: 10.1046/j.1365-2141.1997.442690.x.
Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired haemolytic disorder caused by deficient biosynthesis of the glycosyl phosphatidylinositol (GPI) anchor in haemopoietic stem cells. PIG-A, an X-linked gene that participates in the first step of GPI-anchor synthesis, is responsible for PNH. Various abnormalities of the PIG-A gene have been demonstrated in all patients with PNH so far examined. In this study we characterized the somatic mutations in PIG-A gene in four Taiwanese patients with PNH. We identified five novel mutations in the PIG-A gene, three single nucleotide substitution mutations (-342, C-->G, codon 335, GGT-->AGT and codon 405, GCT-->GTT) and two frameshift mutations (codon 22, GGA-->G-A and codon 356, TGT-->TGTT) in the PIG-A gene. The -342 mutation was judged to be a polymorphism. Furthermore, three patients had previous clinicopathologic evidence which suggested aplastic anaemia (AA), before the development of PNH. One of these was found to have thrombocytopenia during follow-up. We suggest that the somatic PIG-A gene mutations highlight a subgroup of AA having a pathogenetic link with PNH.
阵发性睡眠性血红蛋白尿症（PNH）是一种获得性溶血性疾病，由造血干细胞中糖基磷脂酰肌醇（GPI）锚的生物合成缺陷引起。PIG-A是一个参与GPI锚合成第一步的X连锁基因，与PNH的发生有关。迄今为止，在所有已检测的PNH患者中均发现了PIG-A基因的各种异常。在本研究中，我们对4名台湾PNH患者的PIG-A基因体细胞突变进行了特征分析。我们在PIG-A基因中鉴定出5个新的突变，3个单核苷酸替代突变（-342，C→G；密码子335，GGT→AGT；密码子405，GCT→GTT）和2个移码突变（密码子22，GGA→G-A；密码子356，TGT→TGTT）。-342突变被判定为一种多态性。此外，3名患者在发生PNH之前有提示再生障碍性贫血（AA）的既往临床病理证据。其中1例在随访期间出现血小板减少。我们认为，体细胞PIG-A基因突变突出了一组与PNH有致病联系的AA患者。
