广州市花都地区罕见珠蛋白生成障碍性贫血基因型分布及血液学特征

Genotype distribution and hematological characteristics of rare thalassemia in Huadu area of Guangzhou

目的分析广州市花都地区人群罕见珠蛋白生成障碍性贫血(又称地中海贫血,简称地贫)基因型分布及其血液学特征。方法选择2017年1月至2022年6月在广州市花都区妇幼保健院进行地贫基因检测者的33014例患者的血液标本,分别采用跨越断裂点聚合酶链反应、Sanger测序技术、多重连接探针扩增技术对样本进行α、β地贫基因检测,并对罕见地贫基因型的血液学参数进行统计分析。结果33014例受检者中检测出怀疑为罕见地贫基因型突变样本188例,最终诊断为罕见地贫基因型94例,罕见地贫基因型检出率为0.28%(94/33014);检测出罕见α-地贫基因型46例,11种突变类型,主要包括香港型地贫基因(HKαα)/αα、--^(SEA)/HKαα、-α^(4.2)/HKαα、泰国型地贫基因(--^(THAI))/αα、Fusion gene/αα、CD 40、IVSⅡ-55等。检测出罕见β-地贫基因型48例,8种突变类型,主要包括中国型^(G)γ^(+)(^(A)γδβ)^(0)、东南亚型遗传性持续性胎儿血红蛋白(Hb)增高症(SEA-HPFH)、-90、CD37等。--^(SEA)/HKαα、--^(THAI)/αα的平均红细胞体积(MCV)、平均红细胞血红蛋白含量(MCH)均降低,HbA_(2)正常或降低,而Fusion gene/αα的MCV、MCH处于临界值,HbA_(2)正常。中国型^(G)γ^(+)(^(A)γδβ)^(0)、SEA-HPFH杂合子及复合--^(SEA)/αα基因型的MCV、MCH均降低,HbF均升高,中国型^(G)γ^(+)(^(A)γδβ)^(0)的HbA_(2)正常,而SEA-HPFH的HbA_(2)升高。结论广州市花都地区罕见地贫基因型复杂多样,其血液学具有各自的特征,丰富了该地区的地贫突变谱,对罕见地贫的遗传咨询和产前诊断具有积极的指导作用。

Objective To analyze the genotype distribution and hematological characteristics of a population with rare thalassemia in Huadu area of Guangzhou.Methods A total of 33014 blood samples of thalassemia gene detection in Huadu Maternal and Child Health Hospital of Guangzhou from January 2017 to June 2022 were selected Gap-polymerase chain reaction Sanger sequencing technology and multiplex ligation-dependent probe amplification were used to detect theαandβ-globin genes of the samples,and statistical analysis were performed to the hematological parameters of rare thalassemia genotypes.Results Among the 33014 subjects,188 samples were suspected to be rare thalassemia genotype mutation,and 94 samples were finally diagnosed as rare thalassemia genotype.The detection rate of rare thalassemia genotype was 0.28%(94/33014).A total of 46 samples of rareα-thalassemia genotypes,11 kinds of mutation were detected,which included Hong Kong type thalassemia gene(HKαα)/αα,--^(SEA)/HKαα,-α^(4.2)/HKαα,Thai-style thalassaemia gene(--^(THAI))/αα,Fusion gene/aa,CD40,IVSⅡ-55 and so on,A total of 48 cases of rareβ-thalassemia genotypes,8 kinds of mutation were detected,which included the Chinese ^(G)γ^(+)(^(A)γδβ)^(0) thalassemia,the Southeast Asian hereditary persistent fetal hemoglobin(Hb)(SEA-HPFH),-90,CD37 and soon.Mean corpuscular volume(MCV)and mean corpuscular hemoglobin(MCH)content of--^(SEA)/HKαα and--^(THAI)/αα were decreased,HbA_(2) level was normal or decreased,MCV and MCH of theα-fusion gene were critical and HbA 2 level was in normal range.MCV and MCH were decreased while HbF level was increased when heterozygotes and its composited--^(SEA)/αα of Chinese ^(G)γ^(+)(^(A)γδβ)^(0) and SEA-HPFH,HbA_(2) of Chinese ^(G)γ^(+)(^(A)γδβ)^(0) was normal,while HbA_(2) of SEA-HPFH was increased.Conclusion The genotype of rare thalassemia is complex and diverse in Huadu area of Guangzhou,and its hematology has its own characteristics,which can enrich the mutation spectrum of thalassemia in this region and play a positive guiding role in the genetic counseling and prenatal diagnosis of rare thalassemia.