罕见α-珠蛋白基因突变联合东南亚缺失导致非缺失型Hb H病

韦楠楠; 李琦; 肖璇; 陈萍; 张学

doi:10.16190/j.cnki.45-1211/r.2026.04.002

罕见α-珠蛋白基因突变联合东南亚缺失导致非缺失型Hb H病

Non-deletional hemoglobin H disease caused by rare α-globin gene mutations combined with Southeast Asian deletion

摘要

摘要:
目的分析非缺失型血红蛋白H（hemoglobin H，Hb H）病基因突变类型，探讨不同基因型与临床表型的关系，并分析罕见α-珠蛋白基因突变类型、血液学特征和临床表现，为临床诊疗、遗传咨询和产前诊断提供依据。
方法对2024年1月至2026年1月于广西医科大学第一附属医院进行α-地中海贫血诊疗的病例进行血常规〔血红蛋白（hemoglobin，Hb）、平均红细胞体积（mean corpuscular volume，MCV）、平均红细胞血红蛋白含量（mean corpuscular hemoglobin，MCH）、平均红细胞血红蛋白浓度（mean corpuscular hemoglobin concentration，MCHC）〕的检测和Hb H 分析，应用跨越断裂点聚合酶链式反应（gap-polymerase chain reaction，gap-PCR）、荧光 PCR 熔解曲线法（fluorescence-based PCR melting curve assay，FCMA）、DNA 测序等进行地中海贫血基因分析。
结果 217 例非缺失型Hb H病患者中检出187例Hb Comstant Spring（Hb CS）（--^SEA/α^CSα），27 例Hb Quong Sze （Hb QS）（--^SEA/α^QSα），及 3 例罕见基因突变的Hb H病，包括--^SEA/α^ATG＞GTGα，--^SEA/α^{CD90-92(-AGCTTCGG)}α 和--^SEA/α^CD30(-GAG)α各1例，病例均未合并β-地中海贫血。血常规结果显示，Hb H-CS 组轻度、中度和重度贫血分别占 22.99%、64.71%、12.30%；Hb H-QS 组轻度、中度和重度贫血分别占 44.45%、51.85%、3.70%。基因型--^SEA/α^ATG＞GTGα Hb 107.30 g/L、--^SEA/α^{CD90-92(-AGCTTCGG)}α Hb 88.40 g/L、--^SEA/α^CD30(-GAG)α Hb 73.70 g/L，均伴MCV、MCH 降低。血红蛋白分析结果显示，Hb H-CS 组 Hb H 13.60%（10.45%~15.90%），Hb H-QS组Hb H 23.20%（17.30%~25.00%），二者比较差异有统计学意义（P＜0.05）。--^SEA/α^ATG＞GTGα、--^SEA/α^{CD90-92(-AGCTTCGG)}α 及--^SEA/α^CD30(-GAG)α的Hb H水平分别为25.30%、24.40%、20.40%。
结论非缺失型Hb H病基因型以--^SEA/α^CSα为主，--^SEA/α^QSα 次之。非缺失型Hb H病临床表现中度贫血为主。Hb H-QS组Hb H 水平高于 Hb H-CS组。发现--^SEA/α^ATG＞GTGα、--^SEA/α^{CD90-92(-AGCTTCGG)}α 和--^SEA/α^CD30(-GAG)α 3例Hb H病，临床表现为轻至中度贫血。

Abstract:
Objective To analyze the mutation types of non-deletional hemoglobin H (Hb H) disease, explore the correlation between distinct genotypes and clinical phenotypes, and identify rare α-globin gene mutations, so as to provide evidence for clinical diagnosis and treatment, genetic counseling, and prenatal diagnosis.
Methods Routine blood tests hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and Hb H analysis were performed on patients diagnosed and treated for α-thalassemia at the First Affiliated Hospital of Guangxi Medical University from January 2024 to January 2026. Gap-polymerase chain reaction (gap-PCR), fluorescence-based PCR melting curve assay (FCMA) and DNA sequencing were used for genetic analysis of thalassemia.
Results Among 217 patients with non-deletional Hb H disease, 187 patients were identified as Hb H-CS (--^SEA/α^CSα) and 27 patients as Hb H-QS(--^SEA/α^QSα), and 3 patients carried rare gene mutations causing Hb H disease, including one case each of --^SEA/α^ATG＞GTGα, --^SEA/α^{CD90-92(-AGCTTCGG)}α and --^SEA/α^CD30(-GAG)α. None of the patients were complicated with β-thalassemia. The results of routine blood tests showed that mild, moderate and severe anemia in the Hb H-CS group accounted for 22.99%, 64.71% and 12.30%, respectively; the corresponding proportions of mild, moderate and severe anemia in the Hb H-QS group accounted for 44.45%, 51.85% and 3.70%, respectively. The Hb levels were 107.30 g/L for the --^SEA/α^ATG＞GTGα genotype, 88.40 g/L for the --^SEA/α^{CD90-92(-AGCTTCGG)}α genotype, and 73.70 g/L for the --^SEA/α^CD30(-GAG)α genotype, all accompanied by decreased MCV and MCH. Hb analysis revealed that the Hb H level was 13.60% (10.45%–15.90%) in the Hb H-CS group and 23.20% (17.30%–25.00%) in the Hb H-QS group, with a statistically significant difference between the two groups (P＜0.05). The Hb H levels of the --^SEA/α^ATG＞GTGα, --^SEA/α^{CD90-92(-AGCTTCGG)}α and --^SEA/α^CD30(-GAG)α genotypes were 25.30%, 24.40% and 20.40%, respectively.
Conclusion The predominant genotype of non-deletional Hb H disease is --^SEA/α^CSα, followed by --^SEA/α^QSα. Moderate anemia is the main clinical manifestation of non-deletional Hb H disease. The Hb H level in the Hb H-QS group is higher than that in the Hb H-CS group. Three cases of Hb H disease with genotypes of --^SEA/α^ATG＞GTGα, --^SEA/α^{CD90-92(-AGCTTCGG)}α and --^SEA/α^CD30(-GAG)α are identified, presenting with mild to moderate anemia.

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