Severe inclusion body β-thalassaemia with haemolysis in a patient double heterozygous for β°-thalassaemia and quadruplicated α-globin gene arrangement of the anti-4.2 type

被引:20
作者
Beris, P
Solenthaler, M
Deutsch, S
Darbellay, R
Tobler, A
Bochaton-Pialat, ML
Gabbiani, G
机构
[1] Univ Hosp Geneva, Div Haematol, Geneva, Switzerland
[2] Geneva Sch Med, Dept Pathol, Geneva, Switzerland
[3] Inselspital Bern, Cent Haematol Lab, Bern, Switzerland
关键词
alpha-globin gene quadruplication; inclusion body beta-thalassaemia; alpha/beta mRNA ratio; globin mRNA quantification; thalassaemia intermedia;
D O I
10.1046/j.1365-2141.1999.01451.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We describe a new case of an association of alpha-globin gene quadruplication of the anti-4.2 type with beta degrees-thalassaemia. The patient, a young woman of mixed Brazilian-Portuguese origin, suffered from chronic haemolytic anaemia with splenomegaly. Bone marrow supravital staining with brilliant cresyl blue and electron microscopy studies showed large inclusion bodies in about 3% of erythroblasts. Upon immunofluorescent staining these inclusions reacted with a monoclonal antibody to alpha- but not to beta-globin. Analysis of alpha-globin cluster by Southern blotting showed the presence of pathologic fragments specific for the anti-4.2 alpha-globin gene quadruplication. alpha/beta mRNA ratio was higher than in cases combining alpha-globin triplication and beta degrees-thalassaemia or in cases of beta degrees-thalassaemia heterozygous stale alone (18, 14.7 and 10.1 respectively). Our data confirmed the hypothesis that the clinically detectable haemolysis in this beta degrees-thalassaemic patient was due to an unusually high amount of precipitated alpha-globin in erythroid precursors, This considerable excess of alpha-globin chains was due partly to the beta-globin deficit caused by the presence of the beta degrees-thalassaemic gene, but also to the presence of 6 active alpha-globin genes resulting from alpha-globin gene quadruplication in one chromosome.
引用
收藏
页码:1074 / 1080
页数:7
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