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PIG‐A gene mutations in Four Taiwanese Patients with Paroxysmal Nocturnal Haemoglobinuria Following Aplastic Anaemia
Author(s) -
Lin LiangIn,
Liu ChunHao,
Chen YaoChang,
Shen MingChin,
Wang ChiuHwa,
Huang YiLing,
Lin JenKun
Publication year - 1997
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1997.442690.x
Subject(s) - frameshift mutation , gene , biology , mutation , germline mutation , stop codon , somatic cell , genetics , gene mutation
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.