Li Youqiong, Ye Lihua, Liang Liang, Zheng Lihong, Xiao Yongjun, Lao Zhongchan, Bai Jinping, He Xi, Fang Qixun, Qin Ting
Center for Medical Genetics and Prenatal Diagnosis, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.
Department of Clinical Laboratory, Women and Children Care Hospital of Laibin, Laibin, China.
Front Genet. 2025 May 9;16:1584310. doi: 10.3389/fgene.2025.1584310. eCollection 2025.
δ-thalassemia and δ-globin variants are rare hemoglobinopathies. However, co-inheritance of β-thalassemia and δ-globin gene mutations may affect the diagnosis of β-thalassemia carriers when based on the elevated Hb A. This study aimed to identify and characterize δ-thalassemia and δ-globin variants in Southern China.
Ninety samples with suspected δ-globin gene mutations from 15,642 participants were selected for further molecular analysis based on their Hb A level (≦1.8%) and hematological parameters. Additionally, 37 samples with suspected δ-globin gene mutations were sent from other hospital to our laboratory for identification. GAP-PCR and PCR-reverse dot blot (PCR-RDB) were used to detect common α- and β-thalassemia in the Chinese population, and Sanger sequencing was used to identify δ-globin gene mutations.
Among 15,642 samples examined, samples with δ-globin gene mutations were identified in 127 (0.81%) cases with as many as 28 different genotypes, including 81 (0.52%) cases of δ-thalassemia and 46 (0.29%) cases of δ-globin variants. The most prevalent δ-thalassemia and δ-globin variants of this study were :c.-127T>C (75.3%, 61/81) and Hb A-Melbourne (54.3%, 25/46). Most of the samples were heterozygous (87.4%, 111/127), and only two cases of homozygous were detected. There were three double heterozygotes and 11 cases of combined α/β-globin mutations. Notably, we also identified eight cases of novel mutations in the δ-globin gene. In both heterozygous and homozygous cases, δ-globin mutations maintained hematological parameters within normal ranges, while their co-occurrence with α- or β-thalassemia manifested as a thalassemia phenotype characterized by significantly reduced MCV and MCH values.
The study reveals that δ-globin gene mutations are prevalence in the South China and necessitates integration of δ-globin screening into existing thalassemia prevention protocols.
δ地中海贫血和δ珠蛋白变异是罕见的血红蛋白病。然而，当基于Hb A升高来诊断β地中海贫血携带者时，β地中海贫血和δ珠蛋白基因突变的共同遗传可能会影响诊断结果。本研究旨在鉴定和表征中国南方的δ地中海贫血和δ珠蛋白变异。
根据Hb A水平（≦1.8%）和血液学参数，从15642名参与者中选择90例疑似δ珠蛋白基因突变的样本进行进一步的分子分析。此外，37例疑似δ珠蛋白基因突变的样本从其他医院送至我们实验室进行鉴定。采用缺口聚合酶链反应（GAP-PCR）和聚合酶链反应-反向点杂交（PCR-RDB）检测中国人群中常见的α和β地中海贫血，采用桑格测序法鉴定δ珠蛋白基因突变。
在检测的15642例样本中，127例（0.81%）鉴定出δ珠蛋白基因突变，共有28种不同基因型，其中81例（0.52%）为δ地中海贫血，46例（0.29%）为δ珠蛋白变异。本研究中最常见的δ地中海贫血和δ珠蛋白变异为：c.-127T>C（75.3%，61/81）和Hb A-墨尔本（54.3%，25/46）。大多数样本为杂合子（87.4%，111/127），仅检测到2例纯合子。有3例双杂合子和11例合并α/β珠蛋白基因突变。值得注意的是，我们还在δ珠蛋白基因中鉴定出8例新突变。在杂合子和纯合子病例中，δ珠蛋白突变均使血液学参数维持在正常范围内，而它们与α或β地中海贫血同时出现时，则表现为以MCV和MCH值显著降低为特征的地中海贫血表型。
该研究表明，δ珠蛋白基因突变在中国南方较为普遍，有必要将δ珠蛋白筛查纳入现有的地中海贫血预防方案中。
