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目的鉴定云南德宏地区地中海贫血病例中的基因突变类型和基因型,从而深入阐明该病的临床表型异质性和分子病理机制。方法采用多重缺口PCR技术检测常见的α珠蛋白基因缺失型突变,采用DNA序列测定检测β珠蛋白基因(HBB)中的基因突变和核苷酸变异,对154例云南省德宏地区的地中海贫血进行基因突变检测和基因型分析。结果 154例中有82例呈现α地中海贫血表型,其中71例(86.59%)检测出--SEA、-α3.7和-α4.2三种常见α地中海贫血基因突变,构成5种基因型,-α3.7突变等位基因所占比例最高。有72例为β地中海贫血表型,其中68例(94.44%)检测出-28、CD17、CD26(HbE)、CD41-42、CD71-72、IVS-1-5、IVS-II-654共7种β地中海贫血基因突变,在患者中构成9种β突变基因型;HbE突变等位基因最为多见并与其他β地中海贫血突变形成HbE/β0地中海贫血基因型。在20例β地中海贫血患者中检测到α地中海贫血基因突变,构成10种αβ地中海贫血基因型。在β地中海贫血中还检测到rs713040、rs10768683和rs1609812共3个HBB基因内的SNP位点。结论云南德宏地区的地中海贫血具有明显的遗传异质性,不同基因突变类型的共存和相互作用可能是影响临床表现的主要因素,高的-α3.7和HbE突变等位基因频率是该地区地中海贫血基因型分布的显著特点。
Objective To identify the types and genotypes of genetic mutations in thalassemia cases in Dehong, Yunnan Province, so as to clarify the clinical phenotypic heterogeneity and molecular pathology of the disease. Methods Multiple deletion PCR was used to detect the deletion mutation of α-globin gene. DNA sequencing was used to detect the gene mutation and nucleotide variation in β-globin gene (HBB). A total of 154 cases of thalassemia Gene mutation detection and genotyping. Results 82 out of 154 cases showed α-thalassemia phenotype, of which 71 cases (86.59%) detected three kinds of common α-thalassemia genes, including SEA, -α3.7 and -α4.2, , -α3.7 mutant allele the highest proportion. There were 72 cases with β-thalassemia phenotype, of which 68 (94.44%) detected a total of -28, CD17, CD26 (HbE), CD41-42, CD71-72, IVS-1-5 and IVS-II-654 The mutation of β-thalassemia gene forms nine β-mutation genotypes in patients. The HbE mutation allele is the most common and is mutated with other β-thalassemia to form HbE / β0 thalassemia genotype. Alpha thalassemia mutations were detected in 20 patients with beta-thalassemia, making up to ten alpha beta thalassemia genotypes. In β-thalassemia, three SNB loci were detected in rs713040, rs10768683 and rs1609812. Conclusions Thalassemia in Dehong area of Yunnan Province has obvious genetic heterogeneity. The coexistence and interaction of different gene mutation types may be the main factors affecting clinical manifestations. The frequency of high-α3.7 and HbE mutation alleles is the highest in the region Significant features of the distribution of thalassemia genotypes.