深圳市南山区2 898例地中海贫血基因检测结果分析

目的 研究深圳市南山区地中海贫血基因型和分布特征，探讨检测该病的优化方案。方法 以2017年3月 - 2018年3月在某院进行地中海贫血检测的2 898例就诊者为研究对象，采用跨越断裂点PCR法、反向斑点杂交法和Sanger测序进行基因分析。结果 2 898例受检者中检出地中海贫血基因变异804例，检出率达27.74%。常规地贫基因检测方法检出α-地中海贫血545例，--SEA/αα检出率（11.84%）最高，其次是-α3.7/αα（3.00%）和-α4.2/αα（1.83%）；β-地中海贫血225例，CD41-42（-TTCT）杂合突变和IVS－Ⅱ－654（C＞T）杂合突变为2种检出率最高的突变类型，检出率为3.00%和2.52%；αβ复合地中海贫血30例；Sanger测序分析检出4例少见杂合变异，分别为:HBA1基因上CD5 (GCC＞ACC )；HBB基因CD37G＞A、IVS-Ⅱ-806(G＞C)、IVS-Ⅱ-81C＞T。结论 深圳市南山区地中海贫血发病率较高，基因型与广东省其他地区基本一致。当血液学表型和常规基因检测不相符时，应进行基因测序排除罕见型地中海贫血或异常血红蛋白变异。

Analysis of gene test results of 2898 thalassemia cases in Nanshan district of Shenzhen

Objective The aim of the research is to understand the genotype and distribution characteristics of thalassemia in Nanshan district of Shenzhen,and to optimize its laboratory diagnostic procedure. Methods From March 2017 to March 2018,2 898 patients who were diagnosed with thalassemia in our hospital were selected as the research objects. The methods of gene test included cross breakpoint PCR, reverse spot hybridization method and Sanger sequencing. Results A total of 2 898 test samples of thalassemia genes were successfully collected from patients, among which 804 were diagnosed to be carrying thalassemia gene variants(27.74%). The 804 samples comprise 545 α-thalassemia cases including --SEA/αα (11.84%)，-α3.7/αα (3.00%) and -α4.2/αα(1.83%). 225 β-thalassemia cases in which CD41-42(-TTCT) and IVS-Ⅱ-654(C>T) were the two most frequently detected heterozygous mutations with detection rates of 3.00% and 2.52%, respectively. 30 cases of α and β compound thalassemia. The aforementioned were all diagnosed by routine gene test. The remaining four rare heterozygous variants were HBA1 CD5(GCC>ACC), HBB CD37G>A, HBB IVS-Ⅱ-806(G>C), and HBB IVS-Ⅱ-81C>T detected by using Sanger sequencing. Conclusion The incidence rate of thalassemia is relatively high in Nanshan district. The genotypes in the majority of the cases are largely consistent with the ones in other regions of Guangdong Province. In addition, when normal gene testing results are found to be inconsistent with hemotologic phenotype, gene sequencing is an absolutely indispensable clinical test to effectively reduce the rate of missed diagnosis of rare thalassemia and/or abnormal hemoglobin variants.