【摘要】 目的调查广东省四会市人群中α和β地中海贫血(地贫)的人群发生率和突变基因构成比。方法采集四会市1 007例新生儿脐带血和1 524例婚检成人的外周静脉血,并进行α和β-地贫的分子流行病学调查。α地贫初筛的诊断标准为:Hb Bart’s阳性;β地贫的表型诊断标准为:平均红细胞体积(MCV)<80fl和HbA2≥3.5%。对α和β地贫表型阳性样品进一步进行α和β-珠蛋白基因型的DNA分析,对表型阳性而未查出中国人已知突变基因型的样品进行β-珠蛋白基因DNA序列测定。此外,所有脐带血样品均进行2种静止型α地贫基因(-α3.7和-α4.2)的筛查。结果1 007例脐带血样品中检出110例α地贫基因携带者、3例Hb H病和1例Bart’s水肿胎,人群中α地贫基因携带率11.72%(118 / 1 007)。人群中共检出3种缺失型α地贫基因,其构成比依次为53.4%(--SEA)、34.7%(-α3.7)和11.9%(-α4.2)。1 524例成人外周静脉血样品中检出β地贫携带者59例,所有样品均确定了基因型,检出7种突变类型,人群中β地贫基因携带率为3.87%(59 / 1 524)。在59例β地贫携带者中,有11例(占阳性样品的18.64%)为β地贫复合α地贫病例,人群检出率为0.72%(11 / 1 524)。该地区3种最常见的突变-βCD41-42(-CTTT)移码突变,βIVS-2-654(C→T)剪接突变和β-28(A→G)转录突变占突变基更多还原

【Abstract】 Objective To investigate α- and β-thalassemia (α- and β-thal) gene frequencies and gene mutation spectrum in the population of Sihui City. Methods The umbilical cord blood samples from 1 007 neonates and peripheral blood samples from 1 524 apparently healthy adults for pre-marriage health check in Sihui city were collected for molecular epidemiologic study of α- and β-thal respectively. The diagnostic standard for α-thal was the presence of Hb Bart’s, and that for β-thal was both the decrease of mean corpuscular volume (MCV<80 fl) and the increase of Hb A 2 level (≥3.5%). The samples of identified subjects with positive thal genotypes were further examined with PCR-based DNA analysis for determining the α- or β-globin gene genotype, while those from subjects with positive genotypes but without mutations known to Chinese subjects were sub-jected to DNA sequence analysis of β-globin gene. In addition, the α-thal alleles, -α 3.7 and -α 4.2 , were examined in all umbilical cord blood samples. Results and Conclusion Of all the 1 007 umbilical cord blood samples, 110 were identified as from α-thal gene carriers, 3 from patients Hb H disease and 1 from patients with hydrops fetalis, which meant an α-thal gene fre-quency of 11.72% (118/1 007). Three types of α-gene deletion were identified in this cohort, with the frequency of 53.4% (-- SEA ), 34.7% (-α 3.7 ) and 11.9% (-α 4.2 ) respectively. By examining the peripheral venous blood samples from the 1 524 healthy adult subjects, 59 subjects were found to be β-thal gene carriers with a rate of 3.87% (59/1 524), whose genotypes were deter-mined and from whom 7 β-thal mutations were identified. Of these 59 β-thal gene carriers, 11 were diagnosed as having het-erozygotes compound for β- and α-thal genes with the deletion of the -- SEA in 7 cases and -α 3.7 in 4 cases respectively, showing an incidence of 0.72% (11/1 524). The three commonest point mutations, βCD41-42 (-CTTT) frameshift mutation, βIVS2-654(C→T) aberrant splicing mutation and β-28 (A→G) transcription mutation occurred with a total frequency of 84.75% among subjects with β-thal allele mutations. In ad-dition, a novel mutation, β-globin gene promoter -90 (C→T) allele was detected for the first time in Chinese subjects.更多还原