Somatic deletion of the normal β-globin gene leading to othalassaemia intermedia in heterozygous β-thalassaemic patients

Two β-thalassaemia patients, whose constitutive genotype was β ^39C/β ^39C→T, had the clinical phenotype β-thalassaemia intermedia. Analysis of leucocyte DNA showed the presence of the mutated β ^39C→T-gene exclusively, while the normal β ^39C-gene was also present in reticulocyte RNA. Deletional analysis of chromosome 11p15.5 on leucocyte DNA showed large deletions including the β-globin gene. Two populations of erythroid progenitors, one heterozygous and the other hemizygous for the β ^39C→T mutation, were demonstrated in one case. This confirms that, in heterozygous individuals, β-thalassaemia intermedia may be caused by inactivation of the β-locus in trans as a result of chromosome 11p15.5 deletions in a subpopulation of haematopoietic cells.