云南省德宏地区154例地中海贫血的基因型研究

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。

The genotypes of 154 patients with thalassemia in Dehong prefecture of Yunnan province

Objective To identify gene mutations and genotypes in patients with thalassemia in Dehong Dai and Jingpo autonomous prefecture of Yunnan province, thereby to further elucidate the molecular characterization of the clinical heterogeneity and pathological mechanism of thalassemia in the region. Methods The gene mutations and genotypes in 154 of cases with thalassemia in Dehong prefecture of Yunnan province, were identified by using multiple Gap-PCR for detecting the common alpha globin gene deletions, and using DNA sequencing for identifying beta globin gene mutations and DNA variants. Results In the 154 cases, 82 cases had alpha thalassemia hematological phenotype, in which the common alpha thalassemia mutation--^SEA,-α^3.7 and-α^4.2 were detected in 71 cases（86.59%） and formed 5 genotypes.-α^3.7 was the most common mutant allele. 72 cases presented beta thalassemia phenotype, in which-28, CD17, CD26（HbE）, CD41-42, CD71-72, IVS-1-5 and IVS-II-654 mutations were detected in 68（94.44%） cases and formed 9 genotypes. HbE was the most prevalent and it co-inherited with other β thalassemia mutations to form frequent HbE/β^0-Thalassemia. Alpha thalassemia mutations were found in 20 cases of beta thalassemia patients and formed 10 alpha-beta compound thalassemia genotypes. Three HBB intragenic SNPs, rs713040, rs10768683 and rs1609812, were found in beta thalassemia patients. Conclusions Thalassemia in Dehong prefecture of Yunnan province is highly heterogenic on genotype, the co-existing and interaction among the different mutations could be the major factor affects clinical phenotype of thalassemia. The high frequencies of-α3.7 and HbE alleles are major molecular epidemiological features in Dehong region in Yunnan, China.