罕见缺失型α-珠蛋白基因突变导致α-地中海贫血Hb H病

Hemoglobin H disease caused by a rare deletionalα-globin gene mutation

目的:分析罕见基因突变导致血红蛋白H(Hb H)病的临床和血液学特征。方法:收集2020年5月至2021年2月到广西医科大学第一附属医院就诊、经Hb分析确诊为Hb H病的88例病例,应用跨越断裂点PCR(Gap-PCR)、荧光PCR熔解曲线法(FCMA)检测常见的缺失型和非缺失型α-地中海贫血基因突变,应用二代测序技术检测罕见基因突变。结果:在88例病例中发现3例由-α^(27.6)缺失型突变导致Hb H病的病例,3例均为广西人。病例1为11个月大的女婴,病例2为44岁女性,病例3为10岁男童,3例均表现为中度小细胞低色素贫血,Hb平均值为76.8 g/L,红细胞平均容积(MCV)、红细胞平均血红蛋白量(MCH)、红细胞平均血红蛋白浓度(MCHC)均下降。无黄疸、肝脾肿大和输血史。Hb分析结果显示,3例病例有Hb Bart’s和Hb H,依次为Hb Bart’s 7%,Hb H 4%和Hb H 3%。基因检测结果均显示为α-珠蛋白基因27.6 kb缺失复合东南亚缺失型突变(--^(SEA)/-α^(27.6))。结论:在广西地区发现-α^(27.6)缺失型突变,当复合东南亚缺失型突变可导致Hb H病,临床上表现为中度贫血,Hb分析有Hb Bart’s和Hb H。此类型基因突变较为罕见,容易漏诊,需进一步的基因分析确诊。

Objective:To analyze the clinical and hematological features of rare mutation causing hemoglobin H(Hb H)disease.Methods:A total of 88 cases diagnosed as Hb H disease by hemoglobin analysis were collected in the first Affiliated Hospital of Guangxi Medical University from May 2020 to February 2021.The genotypes ofα-thalassemia were tested by the Gap Polymerase Chain Reaction(Gap-PCR),Fluorescence PCR melting curve analysis and the Next-Generation Sequencing.Results:Three cases of Hb H disease caused by-α^(27.6)deletional mutationwere found among 88 cases,which were from Guangxi province.Case 1 was an 11-month-old girl,Case 2 was a 44-year-old woman,and Case 3 was a 10-year-old boy,who had moderate anemia,with a mean Hb of 76.8 g/L,and a decrease in MCV,MCH,and MCHC.There was no history of jaundice,hepatosplenomegaly or blood transfusion.The results of hemoglobin analysis showed that Hb Bart’s and Hb H in the three cases were 7%,4%and 3%respectively.The results of genotyping showed 27.6 kb deletion combined with Southeast Asian deletion mutation(--^(SEA)/-α^(27.6)).Conclusion:The-α^(27.6)deletional mutation was found in Guangxi province,which might cause Hb H disease when combined with SEA deletional mutation and the clinical manifestation was moderate anemia.Hb analysis showed a small amount of Hb H or Hb Bart’s.This mutation is rare and easy tobe misdiagnosed,which may need further genetic analysis.