A Rare Case of De Novo α-Globin Cluster Duplication, ααα102 (NC_000016.10: G.79903_181947dup) in a β-Thalassemia IVS 1-1 (G>T) (HBB: C.92 + 1G>T) Carrier with Thalassemia Intermedia Phenotype.

α-Globin triplication increases α/non-α-chain imbalance and may lead to a symptomatic β-thalassemia carrier. We describe a novel, de novo large segmental duplication, ααα102 in a patient who is a β-thalassemia IVS 1-1 (G > T) (HBB:c0.92 + 1G > T) carrier and presented with thalassemia intermedia. The duplication spans from intron II, position 203 of the N-methylpurine DNA glycosylase (MPG) gene, to the downstream region of the Hemoglobin Subunit Theta 1 (HBQ1) gene (GRCh38.p14) (HGVS NC_000016.10:g.79903_181947dup). The heterozygous β-thalassemia IVS 1-1 (G > T) was inherited from the father, while the mother was negative for thalassemia. α-MLPA analysis revealed multiple polymorphisms in the father; however, neither parent had the duplication. We concluded that the segmental duplication occurred de novo. In pre-marital screening programs, α-triplications and duplicated α-globin loci should be investigated when one partner has β-thalassemia or a β-thalassemia carrier.