α2珠蛋白基因Codon31(AGG＞AAG)突变导致α地中海贫血的研究

摘要

目的:分析广西地区血红蛋白H病(Hb H病)的基因突变类型,并对先证者进行家系调查.方法:对2016年10月至2017年11月在广西医科大学第一附属医院经血常规、血红蛋白(Hb)分析确诊为Hb H病的360例患者,利用荧光PCR熔解曲线分析法及DNA测序方法进行α地中海贫血基因突变分析.结果:在360例Hb H病患者中发现1例罕见的非缺失型Hb H病.病例为女性,广西北海人,1岁,无黄疸、肝脾肿大等,未输过血.血常规结果显示:RBC 3.75×1012/L,Hb 77.3 9/L,MCV 69.05 fL,MCH 20.62 pg,MCHC 296.9 g/L,HCT 0.26.Hb分析Hb H+-Hb Bart's 20.1％,基因分析结果显示,α2珠蛋白基因Codon 31(AGG＞ AAG)突变复合东南亚缺失型α地中海贫血-1(-SEA/αCCD31 α).患者的家系分析显示,其父亲的血常规及血红蛋白分析正常,基因分析为α2蛋白基因Codon 31突变杂合子.母亲为东南亚缺失型α地中海贫血-1杂合子.结论:首次在广西地区检出α2珠蛋白基因Codon 31 AGG＞AAG基因突变.Codon 31 AGG＞AAG基因突变导致α地中海贫血,当复合东南亚缺失型α地中海贫血-1时有中度贫血.首次发现其杂合子无临床症状,血液学检测正常,临床上较容易误诊和漏诊.%Objective:To analyze the genotypes of hemoglobin(Hb) H disease in Guangxi,and to investigate pedigree state.Methods:360 cases with Hb H disease in our hospital from October 2016 to November 2017 were involved in this study.The genotypes were analyzed by fluorescence PCR analysis and DNA sequencing.Results:Of 360 cases,one case was diagnosed with non-deletional Hb H disease.The case was 1 year old female,a native of Beihai in Guangxi province,who had no jaundice,hepatosplenomegaly and no blood transfusion history.The hematological data revealed RBC 3.75 × 1012/L,Hb 77.3 g/L,MCV 69.05 fL,MCH 20.62 pg,MCHC 296.9 g/L,HCT 0.26.Hb analysis showed 20.1％ of Hb H and Hb Bart's.PCR and DNA sequencing confirmed genotype of a mutation at codon 31(AGG＞AAG) of α2-globin gene and SEA α-thalassemia-1.Family survey suggested that her blood routine test and Hb analysis were normal,and genotype was heterozygote for Codon 31 mutation(AGG＞AAG) on α2-globin gene.While her mother was heterozygote of SEA α-thalassemia-1.Conclusion:This is the first report about the Codon 31 mutation(AGG＞AAG) at 2-globin gene among the Hb H patients in Guangxi province.This mutation may cause α-thalassemia.When co-inherited with SEA α-thalassemia,the patient may have intermediate anemia.But heterozygote for this mutation may have normal hematological data,which is easy to be misdiagnosed without genotyping.