重庆地区28 287例疑似地中海贫血儿童基因检测分析

Genetic testing of children with suspected thalassemia in Chongqing area of China: an analysis of 28 287 cases

摘要:

目的 探讨重庆地区儿童地中海贫血基因检测阳性情况、基因型及分布特征。方法 对2011年1月至2022年12月重庆医科大学附属儿童医院就诊的28 287例经血液学筛查疑似地中海贫血儿童进行常见α和β地中海贫血基因突变位点检测，分析检出率和地中海贫血携带者检出构成比的变化趋势及基因型分布情况。结果 在28 287例疑似地中海贫血儿童中，共检测出15 249例地中海贫血患者，阳性率为53.91%。α、β、αβ地中海贫血阳性率分别为22.41%（6 340例）、30.43%（8 609例）和1.06%（301例），中重型地贫阳性率为2.47%（698例）。2011年至2022年间随年龄增加各组α地中海贫血携带者检出构成比的线性回归k值分别为-0.002、0.004、0.006、0.010、0.012，而β地中海贫血分别为0.011、0.004、0.002、-0.001。共检出21种α地中海贫血基因型，其中α地中海贫血主要基因型为--SEA/αα，占比69.58%。共检测出46种β地中海贫血基因型，其中β地中海贫血主要基因型为CD17/βN、CD41-42/βN及IVS-II-654/βN，占比分别为31.75%、27.92%、25.21%，一共为84.88%。结论 重庆地区儿童地中海贫血常见基因突变位点检测阳性率较高，中重型比例也较高。2011年至2022年间α地中海贫血携带者随年龄段增大检出率升高，而β地中海贫血降低，表明部分β地中海贫血患者基因诊断时间较晚。重庆地区儿童地中海贫血基因型集中在--SEA/αα、CD17/βN、CD41-42/βN及IVS-II-654/βN，与重庆地区成人一致，与广东、广西等地贫高发区有差异。这些结果对于本地区地中海贫血的干预和预防具有重要意义。

Abstract:

Objective To investigate the positive rate of thalassemia genes，genotypes，and distribution characteristics in children in Chongqing area of China.Methods Common α- and β-thalassemia gene mutation sites were detected for 28 287 children with suspected thalassemia who underwent hematological screening at Children’s Hospital of Chongqing Medical University from January 2011 to December 2022，and related analyses were performed to investigate the changing trends of detection rate and the composition ratio of thalassemia carriers，as well as genotype distribution.Results Among the 28 287 children with suspected thalassemia，there were 15 249 children with thalassemia，with a positive rate of 53.91%. The positive rates of α-，β-，and αβ-thalassemia were 22.41%（6 340 cases），30.43%（8 609 cases），and 1.06%（301 cases），respectively，and the positive rate of moderate-to-severe thalassemia was 2.47%（698 cases）. From 2011 to 2022，the linear regression k-values of the composition ratio of α-thalassemia carriers in each age group were -0.002，0.004，0.006，0.010，and 0.012，respectively，while those for β-thalassemia were 0.011，0.004，0.002，and -0.001，respectively. A total of 21 α-thalassemia genotypes were detected，among which --SEA/αα was the main genotype accounting for 69.58%. A total of 46 β-thalassemia genotypes were detected，with the main genotypes of CD17/βN，CD41-42/βN，and IVS-II-654/βN，accounting for 31.75%，27.92%，and 25.21%，respectively，and 84.88% in total.Conclusion There is a relatively high positive rate of common thalassemia gene mutation sites in children in Chongqing area，as well as a relatively high proportion of children with moderate-to-severe thalassemia. From 2011 to 2022，the detection rate of α-thalassemia carriers increases with age，while that of β-thalassemia decreased with age，indicating that some β-thalassemia patients receive genetic diagnosis at an older age. In Chongqing area，the main thalassemia genotypes are --SEA/αα，CD17/βN，CD41-42/βN，and IVS-II-654/βN in children，which are consistent with those in adults，but are different from those in the areas with a high incidence rate of thalassemia，such as Guangdong and Guangxi provinces. These results have significant implications for the intervention and prevention of thalassemia in Chongqing area.