Heterogeneity of the ɛγδβ-thalassaemias: characterization of three novel English deletions

Summary We have characterized three novel ɛγδβ-thalassaemia deletions in three English families. Two of the deletions, 114 and 439 kb, removed the entire β-globin gene complex, including a variable number of flanking olfactory receptor (HOR) genes. The 98-kb deletion extended 90-kb upstream of the ɛ gene to 8 kb upstream of the Gγ-gene, leaving the γ,δ and β-genes intact. The 439 kb deletion is the largest deletion reported so far to cause ɛγδβ-thalassaemia; heterozygotes for this deletion were variably affected by neonatal haemolytic anaemia. Two of the deletions were de novo. Breakpoints of all three deletions occurred within regions of L1 or Alu repeats and contained short regions of direct homology between the flanking sequences, a feature that is likely to have contributed to the illegitimate recombinations.