揭开中间型地中海贫血的神秘面纱：血红蛋白Jax [HBA2:c.44G>C]与缺失性α0-地中海贫血相互作用表型的新发现

IF 1.8 Q3 HEMATOLOGY

Hematology, Transfusion and Cell Therapy Pub Date : 2025-01-01 DOI:10.1016/j.htct.2025.103739

Sitthichai Panyasai , Kanokwan Jaiping , Pisuttinee Khantarag , Patcharee Nochod , Surada Satthakarn

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引用次数: 0

摘要

目的探讨一种不稳定α2-珠蛋白链变异的分子基础、血液学特征、电泳和色谱迁移行为，并探讨其诊断方法。方法对1例泰国不明原因慢性贫血患者及其女儿进行调查。血液学数据分析使用标准的自动细胞计数器。采用高效液相色谱（HPLC）和毛细管电泳（CE）对血红蛋白进行分析。采用适当的聚合酶链反应（PCR）技术和直接测序进行突变分析。并进行α-珠蛋白单倍型分析。开发了简便、快速的诊断方法。结果患者血红蛋白分析显示异常峰分离正常血红蛋白使用高效液相色谱技术可见。这些高峰在女儿身上几乎没有。DNA分析发现，患者α2-珠蛋白基因密码子14的G到C突变，负责血红蛋白Jax转化为α0-地中海贫血基因。在她的女儿身上发现了这种突变的杂合性。血液学分析显示，单纯杂合子轻度地中海贫血样改变，合并α0-地中海贫血时表现为血红蛋白h样表型。异丙醇稳定性测试和生物信息学软件表明，该变异是不稳定的，具有潜在的破坏性。该突变用等位基因特异性PCR证实。血红蛋白Jax与单倍型[+ - S + - + -]密切相关。结论血红蛋白Jax是一种病理性α-珠蛋白变异，在单纯杂合子中无症状，与α-地中海贫血缺失相关时临床效果更明显。这方面的知识可以帮助制定在高流行地区预防血红蛋白病的战略。准确的鉴定需要DNA水平的分析。

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Unraveling thalassemia intermedia: Novel insights of a hemoglobin Jax [HBA2:c.44G>C] and deletional α0-thalassemia interaction phenotype

Objective

To elucidate the molecular basis, hematological features, and electrophoretic and chromatographic mobility behavior of an unstable α₂-globin chain variant, and to describe the diagnostic approach.

Methods

A Thai patient with unexplained chronic anemia and her daughter were investigated. Hematological data were analyzed using a standard automated cell counter. Hemoglobin was analyzed using high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE). Mutational analysis was performed using appropriate polymerase chain reaction (PCR) techniques and direct sequencing. Additionally, α-globin haplotype analysis was conducted. Simple and rapid diagnostic methods were developed.

Results

Hemoglobin analysis in the patient revealed anomalous peaks separated from normal hemoglobin visible using the HPLC technique. These peaks were virtually absent in the daughter. DNA analysis identified a G to C mutation at codon 14 of the α₂-globin gene responsible for hemoglobin Jax in trans to the α⁰-thalassemia gene in the patient. Heterozygosity of this mutation was identified in her daughter. Hematological analysis showed mild thalassemia-like changes in simple heterozygotes and exhibited a hemoglobin H-like phenotype when combined with α⁰-thalassemia. Isopropanol stability testing and bioinformatic software indicated that the variant was unstable and potentially damaging. This mutation was confirmed using allele-specific PCR. Hemoglobin Jax was strongly associated with the haplotype [+ - S + - + -].

Conclusions

Hemoglobin Jax, a pathological α-globin variant, is asymptomatic in simple heterozygotes and demonstrates more pronounced clinical effects when associated with deletional α-thalassemia. This knowledge can help develop strategies to prevent hemoglobinopathies in regions of high prevalence. Accurate identification requires DNA level analysis.

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