β-珠蛋白基因CD114突变导致β-地中海贫血的研究

Study of β-thalassemia caused by mutation of the β-globin gene CD114

目的:研究β-珠蛋白基因CD114(CTG>CCG,HBB:c.344T>C)突变导致β-地中海贫血的血液学特点和临床特征。方法:对地中海贫血筛查疑为β-地中海贫血的病例,采用血细胞常规检测及高效液相色谱法(HPLC)血红蛋白电泳进行血液学表型分析;荧光PCR熔解曲线法、Gap-PCR法和DNA测序进行α-和β-地中海贫血基因分析。结果:共检出440例β-地中海贫血杂合子病例,其中检出1例罕见的β-珠蛋白基因突变杂合子病例,基因分析为β-珠蛋白基因CD114(CTG>CCG,HBB:c.344T>C)杂合子突变。该病例为女性,29岁,有中度贫血,血常规结果:血红蛋白(Hb)78.3 g/L,红细胞(RBC)3.65×10^(12)/L,平均红细胞体积(MCV)66.52 fL,平均红细胞血红蛋白量(MCH)21.48 pg,红细胞平均血红蛋白浓度(MCHC)322.9 g/L。其余439例β-地中海贫血杂合子病例表现为轻度贫血,血常规结果:Hb(115.2±12.46)g/L,RBC(5.79±0.68)×10^(12)/L,MCV(64.27±5.48)fL,MCH(20.10±1.94)pg,MCHC(312.58±8.41)g/L。不同性别的β-地中海贫血杂合子病例血常规分析结果比较,除MCHC外,其他指标差异均有统计学意义(P<0.05)。结论:首次在中国人群中发现罕见β-珠蛋白基因CD114(CTG>CCG,HBB:c.344T>C)突变导致β-地中海贫血。此突变类型罕见,临床上容易漏诊,提示在临床诊疗、遗传咨询和产前诊断过程中要重视这种类型的突变。

Objective:To study the hematological characteristics and clinical features ofβ-thalassemia caused by mutation of theβ-globin gene CD114(CTG>CCG,HBB:c.344T>C).Methods:In cases suspected ofβ-thalassemia by thalassemia screening,routine blood cell testing and hemoglobin electrophoresis by high performance liquid chromatography(HPLC)were applied for hematological phenotyping.Fluorescent PCR melting curve,Gap-PCR and DNA sequencing were used forα-andβ-globin gene analysis.Results:A total of 440 heterozygous cases ofβ-thalassemia were detected,including one rare case of heterozygousβ-hemoglobin gene mutation,which was genetically analyzed as a heterozygous mutation ofβ-hemoglobin gene CD114(CTG>CCG,HBB:c.344T>C).The case was a female,29 years old,with moderate anemia and routine blood results:hemoglobin(Hb)at 78.3 g/L,red blood cells(RBC)at 3.65×10^(12)/L,mean corpuscular volume(MCV)at 66.52 fL,mean corpuscular hemoglobin(MCH)at 21.48 pg,mean corpuscular hemoglobin concentration(MCHC)at 322.9 g/L.The remaining 439β-thalassemia heterozygous cases showed mild anemia with routine blood results:Hb(115.2±12.46)g/L,RBC(5.79±0.68)×10^(12)/L,MCV(64.27±5.48)fL,MCH(20.10±1.94)pg,MCHC(312.58±8.41)g/L.When comparing the results of routine blood analysis ofβ-thalassemia heterozygous cases by gender,the differences were statistically significant(P<0.05)except for MCHC.Conclusion:For the first time,the rareβ-globin gene CD114(CTG>CCG,HBB:c.344T>C)mutation causingβ-thalassemia was identified in a Chinese population.This mutation type is rare and easily missed clinically,suggesting that attention should be paid to this type of mutation during clinical treatment,genetic counseling and prenatal diagnosis.