血红蛋白H病复合非缺失型遗传性胎儿血红蛋白持续存在综合征44例临床分析  

Clinical analysis of 44 hemoglobin H disease cases combined with non-deletional hereditary persistence of fetal hemoglobin

作　　者：邓绍鑫 李树全 肖璇 李琦 罗丹 陈萍 Deng Shaoxin;Li Shuquan;Xiao Xuan;Li Qi;Luo Dan;Chen Ping(Life Sciences Institute,Guangxi Medical University,Nanning 530021,China;NHC Key Laboratory of Thalassemia Medicine,Nanning 530021,China;Key Laboratory of Thalassemia Medicine,Chinese Academy of Medical Sciences,Nanning 530021,China;Guangxi Key Laboratory of Thalassemia Research,Nanning 530021,China)

机构地区：[1]广西医科大学生命科学研究院,南宁530021 [2]国家卫生健康委地中海贫血防治重点实验室,南宁530021 [3]中国医学科学院地中海贫血防治研究重点实验室,南宁530021 [4]广西地中海贫血防治重点实验室,南宁530021

出　　处：《广西医科大学学报》2023年第6期916-921,共6页Journal of Guangxi Medical University

基　　金：国家自然科学基金资助项目(No.81260101);广西重点实验室建设项目(No.22-035-24)。

摘　　要：目的:探讨复合非缺失型遗传性胎儿血红蛋白持续存在综合征(nd-HPFH)对血红蛋白H病(Hb H病)的影响。方法:收集2022年1—12月在广西医科大学第一附属医院进行地中海贫血筛查诊断为Hb H病的患者148例,对研究对象进行血常规检查,采用高效液相色谱法进行血红蛋白(Hb)分析;DNA测序方法检测γ-珠蛋白基因突变;荧光PCR熔解曲线法和Gap-PCR法检测α-和β-地中海贫血基因突变。结果:148例Hb H病患者中,检出44例复合nd-HPFH,检出率为29.7%,基因突变类型为^(G)γ-158C>T突变杂合子27例,^(A)γ-225~-222缺失杂合子13例,^(G)γ-158C>T突变纯合子2例,^(G)γ-158C>T突变杂合子复合^(A)γ-225~-222缺失纯合子1例,^(G)γ-158C>T突变杂合子复合^(A)γ-225~-222缺失杂合子1例。Hb分析结果显示,1例胎儿血红蛋白(Hb F)升高,为5.3%;血常规检查结果:轻度贫血19例,中度贫血24例,重度贫血1例。地中海贫血基因检测结果:--^(SEA)/α^(CS)α20例、--^(SEA)/-α^(3.7)13例、--^(SEA)/-α^(4.2)9例、--^(SEA)/α^(QS)α1例和--THAI/-α^(3.7)1例。结论:nd-HPFH基因突变在Hb H病患者中有较高的检出率,nd-HPFH复合Hb H病临床贫血表现存在差异;此类患者大多数Hb F正常,临床上容易漏诊。Objective:To investigate the effect of compound heterozygous non-deletional hereditary persistence of fetal hemoglobin(nd-HPFH)on hemoglobin H disease(Hb H disease).Methods:A total of 148 patients diagnosed as Hb H disease by thalassemia screening in the First Affiliated Hospital of Guangxi Medical University from January 2022 to December 2022 were collected.Blood routine tests were performed on the subjects,and hemoglobin(Hb)analysis was performed by high performance liquid chromatography.DNA sequencing was used for detecting the mutation ofγ-globin gene.Mutations ofα-andβ-thalassemia genes were detected by fluorescent PCR melting curve analysis and Gap-PCR methods.Results:Among 148 patients with Hb H disease,44 cases with compound nd-HPFH were detected,the gene detection rate was 29.7%,including 27 cases of^(G)γ-158C>T mutant heterozygotes,13 cases of^(A)γ-225 to-222 deletion heterozygotes,2 cases of^(G)γ-158C>T mutant homozygotes,1 case of^(G)γ-158C>T mutant heterozygote combined with^(A)γ-225 to-222 deletion homozygote,1 case of^(G)γ-158C>T mutant heterozygote combined with^(A)γ-225 to-222 deletion heterozygote.The results of Hb analysis showed that 1 case had elevated fetal hemoglobin(Hb F)(5.3%).Blood routine results were as follows:19 cases with mild anemia,24 cases with moderate ane-mia and 1 case with severe anemia.Thalassemia genotyping results were as follows:20 cases with--^(SEA)/α^(CS)α,13 cases with--^(SEA)/-α^(3.7),9 cases with--^(SEA)/-α^(4.2),1 case with--^(SEA)/α^(QS)αand 1 case with--THAI/-α^(3.7).Conclusion:The nd-HPFH mutation has a high detection rate in patients with Hb H disease,and there are differences in clinical anemia in patients with nd-HPFH combined with Hb H disease.Most of these patients have normal Hb F levels and are easy to be missed clinically.

关 键 词：非缺失型遗传性胎儿血红蛋白持续存在综合征 γ-珠蛋白基因 Α-地中海贫血 血红蛋白H病 

分 类 号：R556.7[医药卫生—血液循环系统疾病]