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Genotypic, immunophenotypic and clinical features of Thai patients with paroxysmal nocturnal haemoglobinuria
Author(s) -
Pramoonjago Patcharin,
Pakdeesuwan Kriangsakdi,
Siripanyaphinyo Uamporn,
Chinprasertsuk Sriprapa,
Kinoshita Taroh,
Wanachiwanawin Wanchai
Publication year - 1999
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 - 10.1111/j.1365-2141.1999.01325.x
Subject(s) - cd59 , mutation , phenotype , paroxysmal nocturnal hemoglobinuria , genotype , somatic cell , biology , immunology , germline mutation , hemoglobinuria , gene , complement system , medicine , gastroenterology , genetics , hemolysis , antibody
Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired haematological disorder characterized by complement‐mediated haemolytic anaemia caused by deficiency of glycosylphosphatidylinositol (GPI) anchored proteins. Somatic mutation of an X‐linked gene, PIG‐A, is responsible for the defect in biosynthesis of GPI‐anchor. It appears that frequency of PNH differs geographically, and seems to be more frequent in some Asian countries, such as Thailand and China. We studied a group of 34 Thai patients with PNH to see whether the somatic mutations in PIG‐A, extent of deficiency of GPI‐anchored proteins (complete or partial) and complication with aplastic anaemia among Thai patients are different from those in other regions. We determined 37 PIG‐A mutations in 33 patients (10 base substitutions, 14 single‐base deletions, five multiple‐base deletions, three single‐base insertions, two multiple base insertions and three others) which were found to be similar to those found in European, American and Japanese patients. Most patients had cells with a complete deficiency of CD59 (type III cells), whereas 19% and 33% of the patients with reliable data for CD59 expression had partially deficient granulocytes and erythrocytes (type II cells), respectively. Most mutations resulted in a complete loss of function of PIG‐A in accordance with the prevalent PNH III phenotype. 19 patients (51%) had aplastic anaemia; their PIG‐A mutations were not different from those without pre‐existing aplastic anaemia. These characteristics of Thai patients are similar to patients from other regions. There was some negative correlation between mean basal Hb concentration and percentage of CD59‐negative granulocytes ( r = −0.374; P = 0.0476). In addition, patients with severe anaemia (basal Hb <7 g/dl) had a significantly higher percentage of affected granulocytes than those with mild anaemia (88.5 ± 9.4 v 64.9 ± 25.9; P = 0.01). The data suggest that the severity of anaemia in PNH depends partly on the size of the PNH clone.