Thalassemia intermedia is an inherited hemoglobin disorder characterized by a significant genetic and clinical heterogeneity. A wide spectrum of different genotypes-homozygous, heterozygous, and compound heterozygous-have been found to be responsible for it. The authors describe a Chinese child of β-thalassemia heterozygote with the mutation IVS2-654 (C→T) (HBB:c.316-197C→T) presenting with severe thalassemia intermedia. Multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (CGH) analyses of the α gene cluster revealed an approximate 146-kb duplication at 16p13.3 including the complete α gene cluster. The duplicated allele and the normal allele in trans result in a total of 6 active α genes. The severe clinical phenotype seemed to be related to the considerable excess of the α-globin and the β-globin deficit caused by the presence of the β-thalassemia. The α gene duplication should be considered in patients heterozygous for β-thalassemia who show a more severe phenotype than β-thalassemia trait.
Keywords: CGH; MLPA; α-globin gene duplication; α/β ratio; β-thalassemia.