Large deletions in the β-globin gene cluster lead to increased HbF levels by delaying the γ- to β-globin switch process. However, these deletions when inherited as a homozygous condition or when co-inherited with β-thalassemia result in variable clinical phenotypes. Individuals or families with a clinically presenting child, where the parents had HbF levels ≥ 10%, were further screened for the presence of large β-globin cluster deletions. Six deletions in the β-globin gene cluster were screened by GAP-PCR, and the uncharacterized deletions were further analyzed by gene dosage or by multiplex ligation-dependent probe amplification (MLPA). Among 192 individuals suspected for the inheritance of large deletions, 138 were heterozygous for large deletions, 45 were compound heterozygous of a large β-globin cluster deletion and β-thalassemia, and 9 were found to be homozygous for deletions. Among the heterozygotes, the Asian Indian inversion-deletion was found to be the most common deletion (39.9%), followed by the HPFH-3 deletion (30.0%). Other deletions 49.3 kb, δβ-thalassemia (21.2%), and 32.6 kb deletion (4.4%) were also found to be prevalent in our population. Patients compound heterozygous or homozygous for HPFH-3 and 32.6 kb deletions showed a milder clinical presentation, as compared with the patients compound heterozygous or homozygous for the Asian Indian inversion-deletion and 49.3 kb δβ-thalassemia. This comprehensive study highlights the mutation spectrum of large β-globin cluster deletions and the clinical heterogeneity in the patients homozygous or compound heterozygous with β-thalassemia, thus asserting the need for molecular characterization of these deletions.

β-珠蛋白基因簇中的大量缺失通过延迟 γ- 到 β-珠蛋白的转换过程导致 HbF 水平增加。然而，这些缺失作为纯合子遗传或与 β-地中海贫血共同遗传时会导致不同的临床表型。有临床表现孩子的个人或家庭，其中父母的 HbF 水平≥ 10%，进一步筛查是否存在大的 β-珠蛋白簇缺失。通过 GAP-PCR 筛选出 β-珠蛋白基因簇中的 6 个缺失，并通过基因剂量或多重连接依赖性探针扩增 (MLPA) 进一步分析未表征的缺失。192名疑似大缺失遗传个体中，138人为大缺失杂合子，45人为大β珠蛋白簇缺失与β地贫复合杂合子，和 9 个被发现是纯合的缺失。在杂合子中，发现亚洲印度倒位缺失是最常见的缺失（39.9%），其次是 HPFH-3 缺失（30.0%）。其他 49.3 kb 缺失、δβ-地贫 (21.2%) 和 32.6 kb 缺失 (4.4%) 在我们的人群中也很普遍。与亚洲印度倒位缺失和 49.3 kb δβ-地贫的复合杂合或纯合患者相比，HPFH-3 复合杂合或纯合患者和 32.6 kb 缺失显示出较轻的临床表现。这项综合研究突出了大 β-珠蛋白簇缺失的突变谱和 β-地中海贫血纯合子或复合杂合子患者的临床异质性，因此需要对这些缺失进行分子表征。