5636例疑似地中海贫血样本的异常血红蛋白分子特征及外周血参数分析

Molecular characteristics of abnormal hemoglobin and peripheral blood parameters in 5636 suspected thalassemia samples.

目的 了解可疑罹患(或携带)地中海贫血(简称“地贫”)基因人群中异常血红蛋白基因携带率、异常血红蛋白突变类型及其复合地贫时的分子特征和血细胞参数变化。方法 对中南大学湘雅医学院附属海口医院2016年10月至2022年8月5 636例疑似地贫受试者的样本采用高通量测序技术进行基因检测,对检测出的异常血红蛋白的样本及其血细胞参数进行回顾性分析。结果 5 636例疑似地贫样本中共检出异常血红蛋白46例,检出率为0.82%,突变类型有10种,分别是Hb Owari、Hb HekinanⅡ、Hb Port Phillip、Hb Saclay、Hb New York、Hb Hamilton、Hb J-Bangkok、Hb Shizuoka、Hb Zengcheng和Hb Hachioji;不同异常血红蛋白之间血液表型差异较大,其中Hb New York、Hb HekinanⅡ、Hb Hamilton、Hb Owari、Hb J-Bangkok五组血细胞参数[平均红细胞体积(MCV)、平均红细胞血红蛋白(MCH)、平均红细胞血红蛋白浓度(MCHC)、血红蛋白(Hb)和红细胞分布宽度(RDW)]比较差异均有统计学意义(P<0.05),Hb HekinanⅡ的MCV、MCH、MCHC和Hb平均值最低,Hb Hamilton的四种血细胞参数平均值最高;RDW的数据显示HB New York最高,其次是Hb HekinanⅡ,第三是Hb J-Bangkok,平均值均高于正常范围;性别间的血细胞参数比较差异无统计学意义(P>0.05);异常血红蛋白患者无论是合并α-地贫基因型还是β-地贫基因型,与单纯的异常血红蛋白组相比,血细胞参数差异均无统计学意义(P>0.05)。结论 疑似地贫基因的样本中异常血红蛋白突变类型较多,且有罕见基因型;异常血红蛋白的血细胞参数变化不同,或可为地贫的致病机制找到新的思路。

Objective To investigate the abnormal hemoglobin gene carrying rate,abnormal hemoglobin mutation type,and the changes of molecular characteristics and blood cell parameters in patients with suspected thalassemia gene.Methods The samples of 5636 suspected thalassaemia subjects in Haikou Hospital Affiliated to Xiangya School of Medicine of Central South University from October 2016 to August 2022 were analyzed retrospectively for abnormal hemoglobin and their blood cell parameters using high-throughput sequencing technology for genetic detection.Results A total of 46 cases of abnormal hemoglobin were detected in 5636 suspected thalassaemia samples,and the detection rate was 0.82%.There were 10 types of mutations:Hb Owari,Hb HekinanⅡ,Hb Port Phillip,Hb Saclay,Hb New York,Hb Hamilton,Hb J-Bangkok,Hb Shizuoka,Hb Zengcheng,and Hb Hachioji.The difference of blood phenotype between different abnormal hemoglobin was significant.The blood cell parameters of Hb New York,Hb HekinanⅡ,Hb Hamilton,Hb Owari,and Hb J-Bangkok groups(MCV,MCH,MCHC,Hb and RDW)were significantly different(P<0.05).The mean values of MCV,MCH,MCHC,and Hb of Hb HekinanⅡwere the lowest,while the mean values of four blood cell parameters of Hb Hamilton were the highest.The data of RDW showed that HB New York was the highest,followed by Hb HekinanⅡ,and the average value of Hb J-Bangkok was higher than the normal range.There was no significant difference in blood cell parameters between males and females(P>0.05).There was no significant difference in blood cell parameters between patients with abnormal hemoglobin(whether withα-thalassemia genotype orβ-thalassemia genotype)and patients with only abnormal hemoglobin group(P>0.05).Conclusion There were more abnormal hemoglobin mutations and rare genotypes in the samples suspected of thalassemia gene.The variation of blood cell parameters in abnormal hemoglobin may provide a new idea for the pathogenesis of thalassemia.This study provides effective data for regularly updating the epidemiological investigation of hemoglobinopathies,eugenics and genetic counseling.