深圳地区12960例地中海贫血筛查受检者的地中海贫血基因型分析  

Analysis of thalassemia genotypes in 12 960 thalassemia screened cases in Shenzhen region

作　　者：李玉珠[1] 高素青[1] 史敦云[1] 楼谨[1] 黄瑞宏[1] 黄德善 张琼丽[1] 李明[1] 杜新[1] 

机构地区：[1]广东省深圳市第二人民医院血液病研究所,518035

出　　处：《国际输血及血液学杂志》2016年第3期209-215,共7页International Journal of Blood Transfusion and Hematology

基　　金：深圳市科技计划项目（201203039）

摘　　要：目的探讨深圳地区地中海贫血基因型特征，及其罕见基因型碱基突变位点。方法选择2014年5月至2015年10月于广东省深圳市第二人民医院拟行地中海贫血筛查的12960例受检者为研究对象。研究对象纳入标准：①红细胞平均体积（MCV）〈80fl的门诊及住院患者；②于本院行产前筛查的孕妇。排除标准：①不愿意参加本试验者；②已被确诊为其他血液系统疾病者。受试者先进行血常规MCV、血红蛋白（Hb）电泳和红细胞脆性检测的地中海贫血筛查试验，对筛查试验阳性（红细胞脆性〈70％）的患者，采用跨越断裂点PCR及反向斑点杂交（RDB）技术进行地中海贫血基因常见缺失型和点突变的基因型检测。对常见基因型检测不能确诊的患者，采用巢式PCR和PCR-直接测序（SBT）技术进行罕见基因型分析。本研究遵循的程序符合深圳市第二人民医院制定的伦理学标准，得到该委员会批准，并征得受试对象本人的知情同意，与之签署临床研究知情同意书。结果12960例受检者中，地中海贫血筛查试验阳性患者为2194例，通过常见基因型检测，确诊1019例为地中海贫血，检出率为46．4％。537例a地中海贫血患者中，以东南亚缺失型（--^SEA／αα）比例最高，占66．1％（355／537），其次为α地中海贫血2（-α^3.7／αα）占15．6％（84／537），而基因型（α^CSα／α^CSα、α^QSα／α^Qsα、α^WSα／α^WSα）和4种HbH病基因型（-α^3.7／α^QSα^QS、--^SEA／α^CSα^CS、--SEA／α^QSα^QS、--^SEA／α^WSα^WS）较为少见。α地中海贫血罕见基因型检出率为0．1％（3／2194），包括2例HKαα／^--^SEA及1例HKαα/αα。在456例β地中海贫血患者中，β^41-42（-TCTT）／β和β^654（C〉T）/βA基因型检出率最高，分别为33．8％（154／456）和30．3％（138／456）。在26例β复合α地中海贫血患者中，以p复合a地中海贫血1（--^SEAObjective To explore the characteristics of genotypes and rare gene mutation sites of thalassemia gene in Shenzhen region. Methods From May 2014 to October 2015, a total of 12 960 cases who planned to screen thalassemia in Second People＇s Hospital of Shenzhen were selected as study subjects. The inclusion criteria of this study： （1） Outpatient and hospitalized patients whose mean corpuscular volume （MCV） 〈 80 fl; （2） Pregnant women who did prenatal screening in our hospital. Exclusion criteria： （1）People who did not want to participate in this trial; （2）Patients who had been diagnosed as other diseases of the blood system. Blood samples from all subjects were conducted screening tests including tested by routine blood test MCV, hemoglobin （Hb） electrophoresis, and erythrocyte fragility test. Gap point polymerase chain reaction （PCR） and reverse dot blot （RDB） methods were applied to samples that screening test resutlts were positive （erythrocyte fragility〈 70%）. The unconfirmed cases of thalassemia were applied both the nested PCR method and the PCR-sequence-based typing （SBT） method for the gene sequence analysis. The study protocol was approved by the Ethical Review Board of Investigation in Human Being of Second People＇s Hospital of Shenzhen. Informed consent was obtained from all participants. Results A total of 2 194 patients out of 12 960 cases were positive by thalassemia screening tests, in which 1 019 cases were confirmed through the routine gene sequence analysis, resulting in a detection rate of 46. 4%. Among 537 cases a thalassemia patients, genotype of --^SEA/αα was the most common genotype, accounted for 66.1%（355/537）, followed by α thalassemia 2 genotype （--α^3.7/αα）, accounted for 15.6% （84/537）; and genotype （α^CSα/α^CSα、α^QSα/α^Qsα、α^WSα/α^WSα） and 4 kinds of HbH disease genotype （-α^3.7/α^QSα^QS、--^SEA/α^CSα^CS、--SEA/α^QSα^QS、--^SEA/α^WSα^WS） were rare. Detection rate of a thalassemia r

关 键 词：地中海贫血 聚合酶链反应 基因型 突变 

分 类 号：R556.61[医药卫生—血液循环系统疾病]