PIG-A gene mutations in Four Taiwanese Patients with Paroxysmal Nocturnal Haemoglobinuria Following Aplastic Anaemia |
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Authors: | Liang-In, Lin ,Chun-Hao, Liu ,Yao-Chang, Chen ,Ming-Chin, Shen ,Chiu-Hwa, Wang ,Yi-Ling, Huang & Jen-Kun, Lin |
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Affiliation: | Graduate Institute of Biochemistry; School and Graduate Institute of Medical Technology; Department of Laboratory Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan |
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Abstract: | 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. |
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Keywords: | paroxysmal nocturnal haemoglobinuria aplastic anaemia glycosylphosphatidylinositol (GPI) anchor PIG-A gene |
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