A novel 506 kb deletion causing εγδβ thalassemia

We describe a novel deletion causing εγδβ thalassemia in a Pakistani family. The Pakistani deletion is 506 kb in length, and the second largest εγδβ thalassemia deletion reported to date. It removes the entire β globin gene (HBB) cluster, extending from 431 kb upstream to 75 kb downstream of the ε globin gene (HBE). The breakpoint junction occurred within a 160 bp palindrome embedded in LINE/LTR repeats, and contained a short (9 bp) region of direct homology which may have contributed to the recombination event. Characterization of the deletion breakpoints has been particularly challenging due to the complexity of DNA deletion, insertion and inversion, involving a multitude of methodologies, mirroring the changing DNA analysis technologies.