广西柳州地区β珠蛋白基因的变异分析

Analysis ofβglobin gene variants in Liuzhou area of Guangxi

目的分析广西柳州地区β-珠蛋白生成障碍性贫血(β-地中海贫血)基因型构成及分布情况,为本地区地中海贫血防治工作提供参考。方法对2017年1月至12月到柳州市妇幼保健院进行婚检、产检或体检的13847例受检者,采用反向点杂交技术(reverse dot blot,RDB)检测中国人群常见的17种β-珠蛋白基因点变异,对于筛查结果与人群常见变异类型结果不吻合的病例运用Sanger测序法对其β-珠蛋白基因进行检测。结果13847例受检样本中,检出β-地中海贫血基因变异2098例(15.15%),其中杂合变异2075例(98.90%),复合杂合变异12例(0.57%),纯合变异11例(0.52%),以CD41-42(48.43%)、CD17(31.45%)、IVS-Ⅱ-654(6.33%)型最为常见。β-地中海贫血复合α-地中海贫血共338例,以复合--SEA/αα、-α3.7/αα、αCSα/αα、-α4.2/αα为主。发现β-32/βN,βCD41-42/βIVS-II-5,βCD30/βN等罕见病例。结论广西柳州地区是β-地中海贫血的高发区,其变异谱复杂多样,临床表型也各不相同,与其它地区存在差异。本研究为柳州地区地贫人群进行遗传咨询、产前诊断及制定有针对性的β-地中海贫血防治计划提供数据基础。

Objective To determine the composition and distribution ofβ-thalassemia-associated genotypes in Liuzhou area of Guangxi,China.Methods From January to December 2017,13847 individuals who came for premarital examination,maternity examination or health check were recruited with informed consent.The subjects were analyzed by reverse dot blotting(RDB)for 17 commonβ-thalassemia-associated variants among the Chinese population.Individuals with inconsistent results by blood test,electrophoresis,and RDB were subjected to Sanger sequencing to detect rare variants of the beta globin gene.Results In total 2098 individuals were found to harborβ-thalassemia-associated variants,which included 2075 heterozygotes(98.90%),12 compound heterozygotes(0.57%)and 11 homozygotes(0.52%).CD41-42(48.43%)and CD17(31.45%)were the most common variants.Three hundred and thirty eight-individuals were found to also carry heterozygous variants of the alpha globin gene,with the most common types being--SEA/αα,-α3.7/αα,αCSα/αα,-α4.2/αα.Through Sanger sequencing,rare genotypes such asβ-32/βN,βCD41-42/βIVS-II-5 andβCD30/βN were detected.Conclusion Liuzhou area has a high incidence ofβ-thalassemia,but with a complex variant spectrum and clinical phenotypes different from other regions.Genetic counseling and prenatal diagnosis for the carrier population is crucial for the reduction of the related birth defects.Our result may provide valuable information for the prevention and control ofβ-thalassemia in this area.