β-地中海贫血复合缺失型α-地中海贫血双重杂合子的分子检测及血液学分析

Molecular Detection and Haematological Analysis of Heterozygotes in β-Thalassemia Combining Deletional α-thalassemia

本研究对β-地中海贫血复合缺失型α-地中海贫血双重杂合子进行分子检测及血液学表型分析,以了解其检出情况及基因分布状况。采用单管多重gap-PCR技术检测3种常见的缺失型α-地中海贫血基因;采用PCR结合反向点杂交法检测β-珠蛋白基因17个位点的18种突变;进行血细胞常规分析。结果表明:81例β-地中海贫血杂合子中有15例复合缺失型α-地中海贫血,占18.52%。共有9种基因型,包括6例(7.41%)β-地中海贫血杂合子携带α-地中海贫血-1基因(--SEA/αα);8例(9.88%)携带α-地中海贫血-2基因,其中6例(7.41%)为右侧缺失型(-α3.7/αα),2例(2.47%)为左侧缺失型(-α4.2/αα);1例(1.23%)携带缺失型HbH基因(--SEA/-α3.7)。β-地中海贫血复合缺失型α-地中海贫血双重杂合子的各项红细胞参数与单纯β-地中海贫血杂合子比较差异无显著性意义(P>0.05)。结论:梧州市β-地中海贫血复合缺失型α-地中海贫血双重杂合子的发生率很高,而血液学指标缺乏特异性。采用gap-PCR作为临床上地中海贫血筛查的一线方法,可以有效减少β-地中海贫血复合α-地中海贫血双重杂合子漏检的可能,对遗传咨询和准确进行产前诊断具有重要意义。

This study was aimed to investigate the prevalence and genotype distribution of heterozygotes in β- thalassemia combining deletionai α-thaiassemia by using molecular detection and haematologicai methods. Three common deletions of α-thaiassemia were detected by using gap-PCR. The mutations of β-thaiassemia were identified by using PCR with reverse dot blot hybridization. The routine analysis of blood cells was carried out. The results indicated that 15 cases from the 81 β-thaiassemia traits were found to be the compound heterozygosity for β-thaiassemia and α- thalassemia with 9 different types of gene defects with 18.52% detection rate. There were 6 cases （7.41%） of β- thalassemia heterozygote combining α-thaiassemia-1 gene（--SEA/act）, 8 cases （9.88%） combining with α-thalassemia- 2 gene including 6 （7.41%） right ward deletion（-α^3.7/αα ） and 2 （2.47%） left ward deletion（-α^4.2/αα）, and 1 case （1.23%） combining deletionai HbH gene （--^SEA/-α^3.7）. NO signifiCant differences were found between β-thalassemia heterozygotes combining deletionai α-thaiassemia and pure β-thaiassemia in all RBC parameters. It is concluded that the incidence of β-thalassemia heterozygotes combining with deletionai α-thaiassemia is frequent in Wuzhou city. The hematological analysis can not give specificity for diagnosing these dual heterozygotes. Gap-PCR as a routine method for thalassemia screening has the advantages in reducing the possibility of failing to detect the combining heterozygosity for β-thalassemia and α-thalassemia. It is more useful for genetic counselling and prenatal diagnosis of this disease.