CAJ | 학술논문

目的探讨在中国人群中发现的1个少见β地中海贫血家系的分子遗传学特征.方法采用标准的血液学分析技术检测先证者及家系成员红细胞参数,包括RBC、Hb、MCV、MCH、MCHC和RDW,进行表型诊断.利用SPIFE快速自动电泳分析系统检测其血红蛋白组分Hb A、Hb A2和Hb F.采用RDB技术检测β地中海贫血基因突变,并进一步进行克隆测序及家系分析,明确突变位点.结果先证者及其父亲红细胞参数呈典型的小细胞低色素改变,MCV和MCH均降低,MCV分别为79.1 fl及63.1 fl,MCH为19.9 pg及20.9 pg;而先证者母亲的MCV及MCH均正常.先证者及其父亲Hb A2增加,分别为5.66%及5.60%,提示其为轻型β地中海贫血基因携带者.进一步的基因分析表明,先证者在一个β珠蛋白基因同时发生CD41/42(-TTCT)和转录区+40～+43缺失突变,诊断为β41/42、CAP/βA基因型的轻型地中海贫血患儿,其父母基因型分别为β41/42、CAP/βA 和βA/βA.结论先证者在一个β珠蛋白基因同时发生CD41/42(-TTCT)和转录区+40～+43缺失突变,β41/42、CAP/βA基因型的发现丰富了中国人群β珠蛋白基因突变研究数据,有助于β地中海贫血的起源和演变的研究.
목적 탐토재중국인군중발현적1개소견β지중해빈혈가계적분자유전학특정.방법 채용표준적혈액학분석기술검측선증자급가계성원홍세포삼수,포괄RBC、Hb、MCV、MCH、MCHC화RDW,진행표형진단.이용SPIFE쾌속자동전영분석계통검측기혈홍단백조분Hb A、Hb A2화Hb F.채용RDB기술검측β지중해빈혈기인돌변,병진일보진행극륭측서급가계분석,명학돌변위점.결과 선증자급기부친홍세포삼수정전형적소세포저색소개변,MCV화MCH균강저,MCV분별위79.1 fl급63.1 fl,MCH위19.9 pg급20.9 pg;이선증자모친적MCV급MCH균정상.선증자급기부친Hb A2증가,분별위5.66%급5.60%,제시기위경형β지중해빈혈기인휴대자.진일보적기인분석표명,선증자재일개β주단백기인동시발생CD41/42(-TTCT)화전록구+40～+43결실돌변,진단위β41/42、CAP/βA기인형적경형지중해빈혈환인,기부모기인형분별위β41/42、CAP/βA 화βA/βA.결론 선증자재일개β주단백기인동시발생CD41/42(-TTCT)화전록구+40～+43결실돌변,β41/42、CAP/βA기인형적발현봉부료중국인군β주단백기인돌변연구수거,유조우β지중해빈혈적기원화연변적연구.
Objective To investigate the molecular characterization of a Chinese pedigree with rare β thalassemia genotype.Methods Phenotypic analysis was performed using standard hematological tests to measure red blood cell parameters, including RBC,Hb,MCV,MCH,MCHC and RDW.SPIFE automatic Hb agarose gel electrophoresis instrument was used to measure hemoglobin fraction Hb A,Hb A2 and Hb F.The alleles of β thalassemia mutation were determined by RDB assay, and then cloning and sequencing were performed to define the mutation sites.Results The proband and his father had typical microcytic hypochromic anemia with low MCV and MCH(79.8, 63.1 fl and 19.9, 20.9 pg, respectively) and high level of Hb A2 (5.66% and 5.60%, respectively).The proband′s mother had normal MCV and MCH. β thalassemia mutation analysis with RDB assay showed that the proband had thalassemia minor resulting from double mutations on one globin gene.One showed codons 41/42 (-TTCT) mutation and the other was CAP mutation from positions +40 to +43 in the promoter region.These two mutations were inherited from his father.The genotype of the proband and his father was β41/42、CAP/βA ,and the genotype of his mother was βA/βA.Conclusions It′s rare that double mutations occur on single β globin gene, with one mutation on CD41/42(-TTCT) and the other mutation from positions +40 to +43 relative to the mRNA cap site in the promoter region.The findings enrich knowledge of the mutation spectrum of β thalassemia.