A novel mechanism for thalassaemia intermedia

Association of globin gene quadruplication and heterozygous thalassemia in patients with thalassemia intermedia

“…[1][2][3] Less commonly, the phenotype of thalassemia intermedia has been reported in subjects carrying only one β globin gene defect. Among them 3 groups have been defined: (i) the dominantly inherited β thalassemia mutations (also reported as inclusion body thalassemias); 4,5 (ii) the co-existence of somatic deletions of a region of chromosome 11 p15; 6,7 (iii) co-inheritance of triplicated α globin genes with excessive α globin production. [8][9][10] Recently cases of simple β thalassemia heterozygosity presenting with an intermediate to severe phenotype due to duplications of the complete α globin gene cluster, including the upstream regulatory element HS-40, have been reported; 11 (iv) interaction between severe and silent β thalassemia mutations.…”

-thalassemia major evolution from -thalassemia minor is associated with paternal uniparental isodisomy of chromosome 11p15

“…Because the acquired chromosome 11p15.5 deletion is frequently observed in a variety of malignancies, 8 and acquired deletion of the HBB gene is also described by Badens and by Galanello et al, 9,10 we suspected that the patient may have a hemizygosity caused by acquired deletion of chromosome 11p15.5 harboring the HBB gene. However, FISH analysis showed that both chromosome 11s had positive hybridization signals with all three probes studied (β-LCR, HBG and HBB gene probes), indicating that the HBB gene cluster was probably intact ( Figure 1B).…”

Mosaic segmental uniparental isodisomy and progressive clonal selection: a common mechanism of late onset -thalassemia major

“…Beta-thalassemia intermedia patients with a mitotic LoH in the hematopoietic lineage due to a deletion containing the unaffected β-globin gene has been reported by Badens et al and Galanello et al 8,9 Somatic deletions giving rise to loss of heterozygosity have been discovered and studied in the context of carcinogenesis. 10,11 However, as MLPA and Illumina SNP array analysis showed no deletion involving the β-globin gene or neighboring region in the DNA isolated from blood of any of these independent patients, another molecular cause was expected.…”