柳州市城镇人群α和β地中海贫血的发生率调查和基因型鉴定

目的 调查广西柳州市城镇人口中α和β地中海贫血（地贫）的发生率和基因突变类型及其构成比。方法 以整群抽样收集1028份其父母双方或一方为柳州市户口的新生儿脐带血及1312份柳州市户口的婚检育龄成人的外周静脉血，分别进行α地贫和β地贫调查；所有样品均进行红细胞（RBC）参数和血红蛋白（Hb)电泳分析，以巴特血红蛋白（Hb Bart's)阳性者为α地贫，平均红细胞体积（MCV＜85fl和HbA2≥4．0％为β地贫阳性表型指标。采用基于PCR的基因分析方法进行α和β地贫及β地贫复合α地贫样品的确诊，对α和β地贫表型阳性而未查出基因者，以家系成员的表型分析诊断。结果 1028份脐带血样品检出α基因携带者112例（包括3例双重杂合子），α地贫基因携带率11．19％，共检出含5种α地贫的等位基因，其构成比依次为37．4％（－－^SEA),31.3%(-α^3.7),17.4%(-α^4.2),12.1%(α^CSα)和0．9％（α^QSα)。1312份成人外周静脉血样品共发现β地贫携带者89例，基因携带率为6．78％。其中有14例伴有胎儿血红蛋白（HbF)增高，检出率1．07％。在89例β地贫阳性样品中，有16例（占18％）为β地贫复合α地贫双重杂合子，共发现9种不同的基因型，检出率为1．22％。该地区3种最常见的基因－βCD41－42（－CTTT）移码突变，βCD17（T－A）无义突变和β－28（A－G）转录突变占突变基因的90％。结论 α和β地中海贫血在柳州地区的发生率很高。

Prevalence survey and molecular characterization of α and β thalassemia in Liuzhou city of Guangxi

OBJECTIVE: To investigate the gene frequencies and mutation patterns of alpha thalassemia (alpha-thal) and beta thalassemia (beta-thal) in Liuzhou city of Guangxi Zhuang Autonomous Region. METHODS: Cluster sampling was used. A total of 1 028 of umbilical blood samples were collected for a prevalence study of alpha-thal and a total of 1 312 healthy young people when receiving pre-marriage consultation were recruited for a beta-thal prevalence survey. Individuals live in city or town area of Liuzhou. A complete blood count as well as hemoglobin electrophoresis analysis were done in all of samples for phenotyping of alpha and beta-thals. Those with Hb Bart's for alpha-thal indicator and those with both microcytosis (MCV < 85 fl) and elevated levels of Hb A(2) (>/=4.0%) for beta-thal were further studied by DNA analysis. PCR-based methodologies were used to characterize the mutation contributions of alpha and beta-thals. All the subjects were tested for the state of carrying beta-thala alleles for evaluating the situation of the compound heterozygotes of alpha-thal with beta-thal. RESULTS: Of 1 028 random samples of umbilical blood screened, 112 of subjects were defined to be the gene carriers of alpha-thal. The alpha-thal carrier rate was as high as 11.19% including 3 compound heterozygotes. Five well-known types of alpha-thal alleles were detected with gene contributions of 37.4% (--(SEA) deletion), 31.3% (-alpha(3.7) deletion), 17.4% (-alpha(4.2) deletion), 12.1% (alpha(CS)alpha mutation), and 0.9% (alpha(QS)alpha mutation), successively. Of the 1 312 adult specimens studied, 89 with beta-thal including 14 of the compound higher Hb F subjects were detected. All of the 89 phenotypic beta-thal carriers had the mutations in the beta-globin gene, making the overall prevalence 6.78%. The commonly seen three mutations, beta CD41 - 42 (-CTTT) frameshift, beta CD17 (T-A) nonsense mutation and beta-28 (A-G) promoter variation were accounted for 90% of the beta-thal alleles in Liuzhou. Of these beta-thal subjects, 16 (accounting for 18%) were found to be the compound heterozygosity for a beta-thal and an alpha-thal with 9 different types of gene defects with a detection rate 1.22%. CONCLUSION: Data from ecidation of alpha and beta-thal gene frequencies and mutation spectrum in Liuzhou city was useful for genetic counselling and prenatal diagnosis of this disease.