Screening for common β-globin gene cluster deletions in Chinese individuals with increased hemoglobin F

Introduction: The aim of this study was to determine the prevalence of beta-globin gene cluster deletions in individuals with increased Hb F levels in a Chinese population. Methods: Subjects with HbF levels >= 10% were selected for further investigation. Gap-PCR was used to screen for three common beta-globin gene cluster deletions: Chinese ((A)gamma delta beta)(0)-thalassemia, Southeast Asian (SEA) deletion and Hb Lepore. Multiplex ligation-dependent probe amplification (MLPA) was used to analyze dosage changes of the beta-globin gene cluster for those not associated with one of the three common deletions. Results: One hundred and thirty-one individuals had an increased Hb F level; among these, 51 (38.9%) were showed to have Chinese ((A)gamma delta beta)0-thalassemia (n = 37) or SEA deletion (n = 14). A single case of Hb Lepore-Boston-Washington was detected. MLPA only detected 2 deletions in three cases of the remaining 80 patients. Gap-PCR confirmed that they included a 1357 bp beta-globin gene deletion (NG_000007.3: g.69997_71353del1357) in one case and a HBG2-HBG1 fusion gene consisting of exons 1 and 2 of HBG2 ((G)gamma-globin gene) and exon 3 of HBG1 ((A)gamma-globin gene) (HBG2: c.315 + 573_HBG1: c.315 + 572del) in two cases. Conclusion: The Chinese ((A)gamma delta beta)0-thalassemia and SEA deletion are the most common large deletions of beta-globin gene cluster in Chinese. Gap-PCR for the detection of these two deletions should be used in thalassemia screening program in China where the incidence of beta-thalassemia is high.