CAJ | 학술논문

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。
목적：감정운남덕굉지구지중해빈혈병례중적기인돌변류형화기인형，종이심입천명해병적림상표형이질성화분자병리궤제。방법채용다중결구PCR기술검측상견적α주단백기인결실형돌변，채용DNA서렬측정검측β주단백기인（HBB）중적기인돌변화핵감산변이，대154례운남성덕굉지구적지중해빈혈진행기인돌변검측화기인형분석。결과154례중유82례정현α지중해빈혈표형，기중71례（86.59%）검측출--SEA、-α3.7화-α4.2삼충상견α지중해빈혈기인돌변，구성5충기인형，-α3.7돌변등위기인소점비례최고。유72례위β지중해빈혈표형，기중68례（94.44%）검측출-28、CD17、CD26（HbE）、CD41-42、CD71-72、IVS-1-5、IVS-II-654공7충β지중해빈혈기인돌변，재환자중구성9충β돌변기인형；HbE돌변등위기인최위다견병여기타β지중해빈혈돌변형성HbE/β0지중해빈혈기인형。재20례β지중해빈혈환자중검측도α지중해빈혈기인돌변，구성10충αβ지중해빈혈기인형。재β지중해빈혈중환검측도rs713040、rs10768683화rs1609812공3개HBB기인내적SNP위점。결론운남덕굉지구적지중해빈혈구유명현적유전이질성，불동기인돌변류형적공존화상호작용가능시영향림상표현적주요인소，고적-α3.7화HbE돌변등위기인빈솔시해지구지중해빈혈기인형분포적현저특점。
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,-α3.7 and-α4.2 were detected in 71 cases (86.59%) and formed 5 genotypes. -α3.7 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/β0-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.