The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.
Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center affiliated with Guangzhou Medical University, Guangzhou, Guangdong Province, People's Republic of China.
BMC Med Genet. 2020 Feb 28;21(1):43. doi: 10.1186/s12881-020-0981-x.
Individuals with δβ-thalassemia/HPFH and β-thalassemia usually present with intermedia or thalassemia major. No large-scale survey on HPFH/δβ-thalassemia in southern China has been reported to date. The purpose of this study was to examine the molecular epidemiology and hematologic characteristics of these disorders in Guangzhou, the largest city in Southern China, to offer advice for thalassemia screening programs and genetic counseling.
A total of 125,661 couples participated in pregestational thalassemia screening. 654 subjects with fetal hemoglobin (HbF) level ≥ 5% were selected for further investigation. Gap-PCR combined with Multiplex ligation dependent probe amplification (MLPA) was used to screen for β-globin gene cluster deletions. Gene sequencing for the promoter region of HBG1 /HBG2 gene was performed for all those subjects.
A total of 654 individuals had hemoglobin (HbF) levels≥5, and 0.12% of the couples were found to be heterozygous for HPFH/δβ-thalassemia, including Chinese γ (γδβ)-thal, Southeast Asia HPFH (SEA-HPFH), Taiwanese deletion and Hb Lepore-Boston-Washington. The highest prevalence was observed in the Huadu district and the lowest in the Nansha district. Three cases were identified as carrying β-globin gene cluster deletions, which had not been previously reported. Two at-risk couples (0.0015%) were required to receive prenatal diagnosis. We also found 55cases of nondeletional-HPFH (nd-HPFH), including 54 with Italian nd-HPFH and one with the γ-197C-T heterozygous state. It is difficult to discriminate between Chinese γ (γδβ)-thal and Italian nd-HPFH carriers using hemoglobin (Hb) analysis.
This study is the first to describe the familial prevalence of HPFH/δβ-thalassemia and the high-risk rate in Greater Guangzhou Area, and the findings will support the implementation of thalassemia screening for three common deletions by gap-PCR. We also presented a systematic description of genotype-phenotype relationships which will be useful for genetic counseling and prenatal diagnostic services for β-thalassemia intermedia.
δβ-地中海贫血/血红蛋白持续高表达与β-地中海贫血患者通常表现为中间型或重型地中海贫血。目前尚未有报道称在中国南方地区进行了大规模的血红蛋白持续高表达/δβ-地中海贫血调查。本研究旨在探讨中国南方最大城市广州地区这些疾病的分子流行病学和血液学特征，为地中海贫血筛查计划和遗传咨询提供建议。
共有 125661 对夫妇参加了孕前地中海贫血筛查。选择 654 名胎儿血红蛋白（HbF）水平≥5%的受试者进行进一步调查。采用Gap-PCR 联合多重连接依赖性探针扩增（MLPA）技术筛查β-珠蛋白基因簇缺失。对所有受试者的 HBG1/HBG2 基因启动子区进行基因测序。
共有 654 名个体的血红蛋白（HbF）水平≥5，发现 0.12%的夫妇为血红蛋白持续高表达/δβ-地中海贫血杂合子，包括中国γ（γδβ）-地中海贫血、东南亚血红蛋白持续高表达（SEA-HPFH）、台湾缺失和 Hb Lepore-Boston-Washington。花都区的发病率最高，南沙区的发病率最低。发现 3 例β-珠蛋白基因簇缺失，这是以前未报道过的。有 2 对高危夫妇（0.0015%）需要进行产前诊断。我们还发现了 55 例非缺失型血红蛋白持续高表达（nd-HPFH），其中 54 例为意大利 nd-HPFH，1 例为γ-197C-T 杂合状态。用血红蛋白分析很难区分中国γ（γδβ）-地中海贫血和意大利 nd-HPFH 携带者。
本研究首次描述了大广州地区血红蛋白持续高表达/δβ-地中海贫血的家族患病率和高危率，研究结果将支持采用 Gap-PCR 对三种常见缺失进行地中海贫血筛查。我们还系统地描述了基因型-表型关系，这将有助于β-地中海贫血中间型的遗传咨询和产前诊断服务。
