标题：5 636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

      作者：王婵，黄邓高，冯女，张淑芳，刘海芳，唐小燕，陈扬    王婵，黄邓高，冯女，张淑芳，刘海芳，唐小燕，陈扬中南大学湘雅医学院附属海口医院中心实验室海口市临床医学重点实验室，海南 海口 570208

      卷次： 2024年35卷4期

      【摘要】 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 Hamil-ton、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HbNew 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。
      【关键词】 海口；异常血红蛋白；地中海贫血；高通量测序；血液学指标
      【中图分类号】 R556 【文献标识码】 A 【文章编号】 1003—6350（2024）04—0521—06

Molecular characteristics of abnormal hemoglobin and peripheral blood parameters in 5 636 suspectedthalassemia samples.
WANG Chan, HUANG Deng-gao, FENG Nv, ZHANG Shu-fang, LIU Hai-fang, TANG Xiao-yan,CHEN Yang. Central Laboratory, Haikou Hospital Affiliated to Xiangya School of Medicine of Central South University/Haikou Key Laboratory of Clinical Medicine, Haikou 570208, Hainan, CHINA
【Abstract】 Objective To investigate the abnormal hemoglobin gene carrying rate, abnormal hemoglobin muta-tion type, and the changes of molecular characteristics and blood cell parameters in patients with suspected thalassemiagene.Methods The samples of 5 636 suspected thalassaemia subjects in Haikou Hospital Affiliated to Xiangya School ofMedicine of Central South University from October 2016 to August 2022 were analyzed retrospectively for abnormal he-moglobin and their blood cell parameters using high-throughput sequencing technology for genetic detection. Results Atotal of 46 cases of abnormal hemoglobin were detected in 5 636 suspected thalassaemia samples, and the detection ratewas 0.82%. There were 10 types of mutations: Hb Owari, Hb HekinanⅡ, Hb Port Phillip, Hb Saclay, Hb New York, HbHamilton, Hb J-Bangkok, Hb Shizuoka, Hb Zengcheng, and Hb Hachioji. The difference of blood phenotype betweendifferent abnormal hemoglobin was significant. The blood cell parameters of Hb New York, Hb HekinanⅡ, Hb Hamil-ton, 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 HekinanⅡ were the lowest, while the mean values of four bloodcell parameters of Hb Hamilton were the highest. The data of RDW showed that HB New York was the highest, followedby Hb HekinanⅡ, and the average value of Hb J-Bangkok was higher than the normal range. There was no significantdifference in blood cell parameters between males and females (P>0.05). There was no significant difference in bloodcell parameters between patients with abnormal hemoglobin (whether with α-thalassemia genotype or β-thalassemiagenotype) and patients with only abnormal hemoglobin group (P>0.05). Conclusion There were more abnormal hemo-globin mutations and rare genotypes in the samples suspected of thalassemia gene. The variation of blood cell parametersin abnormal hemoglobin may provide a new idea for the pathogenesis of thalassemia. This study provides effective datafor regularly updating the epidemiological investigation of hemoglobinopathies, eugenics and genetic counseling.
      【Key words】 Haikou; Abnormal hemoglobin; Thalassemia; High-throughput sequencing; Hematological indicators