Abnormal hemoglobin anti-Lepore Hong Kong compound with β0-thalassemia ameliorate thalassemia severity when co-inherited with a-thalassemia

Background: Abnormal hemoglobin anti-Lepore Hong Kong is rare βδ fusion variants resulted from non-homologous crossover during meiosis. Anti-Lepore Hong Kong always showed extraordinary increased HbA2. In this study, we used multiplex ligation-dependent probe amplification (MLPA) and single molecular real time (SMRT) sequencing, as well as Sanger sequencing, to detect variants in five unrelated families with abnormal increased HbA2 level. Results: All the probands in these five families were detected with anti-Lepore Hong Kong heterozygotes. Among them, two families were compounded with β 0 -thalassemia and α-thalassemia (-- SEA / or α CS α/). The heterozygotes of anti-Lepore Hong Kong had an average 17.7% of HbA2 level and behaved normal. However, when compounded with β 0 -thalassemia and α-thalassemia, the probands had higher HbA2 level (30.2%-40.8%) and behaved with β-thalassemia trait. Moreover, the determination of α/β-mRNA ratio showed a slightly downregulation of β-globin, similar to that of β-thalassemia minor. Conclusions: Our study first identifies the compound heterozygotes with anti-Lepore Hong Kong and β 0 -thalassemia and α-thalassemia, and provide better information in prenatal counseling.