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/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HbH 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）}α3例HbH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 testshemoglobin（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 nondeletional 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）}αgenotype,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）}αand --^SEA/α^{CD30（-GAG）}α are identified,presenting with mild to moderate anemia.

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