A novel beta-delta globin gene fusion, anti-Lepore Hong Kong, leads to overexpression of delta globin chain and a mild thalassaemia intermedia phenotype when co-inherited with β0-thalassaemia

Anti-Lepore haemoglobins (Hb) are rare βδ fusion variants that arise from non-homologous crossover during meiosis, resulting in a δ-βδ-β configuration. A novel anti-Lepore mutation (anti-Lepore Hong Kong) was found in two Chinese families with raised Hb A 2. Direct sequencing revealed a crossover within a 54-bp region spanning the junction of cap site (CAP) and exon 1, which predicted the production of normal δ-globin. Determination of α/β-mRNA ratios by quantitative real-time polymerase chain reaction demonstrated downregulation of the β gene in cis due to the interposed βδ fusion gene. Although heterozygotes have normal red cell indices and are clinically silent, compound heterozygotes with β0 mutation in trans produce a mild thalassaemia intermedia phenotype with a markedly raised Hb A2 level that may mimic clinically mild Hb E-β+-thalassaemia. Awareness of the presence of anti-Lepore Hong Kong will help to resolve diagnostic problems in regions with significant prevalence of globin disorders. © 2007 The Authors.link_to_OA_fulltex