湖北省育龄人群地中海贫血基因变异类型及分布特征

Genetic variation and distribution characteristics of thalassemia in people of childbearing age in Hubei Province

目的了解湖北省育龄人群地中海贫血(简称地贫)基因的检出情况及分布特点,为湖北省地贫防控政策制定和推广应用提供一定的临床依据。方法收集2019年5月13日至2021年8月17日湖北省相关医院接收的44849例育龄人群的静脉血样本,采用PCR-流式荧光杂交法和PCR+导流杂交法进行地贫基因筛查;同时,对筛查阳性者的配偶也进行地贫基因检测。当夫妻双方携带同一类型地贫基因时,抽取妊娠妇女羊水进行产前诊断,并进行随访。结果在44849例育龄人群中,2286例经基因检测确诊为地贫基因携带者,总检出率为5.10%(2286/44849)。其中,α地贫1488例,检出率为3.32%(1488/44849);β地贫767例,检出率为1.71%(767/44849);α地贫合并β地贫31例,检出率为0.07%(31/44849)。α地贫基因突变类型构成比前3位依次为-α^(3.7)/αα、--^(SEA)/αα、-α^(4.2)/αα,分别占58.06%(864/1488)、26.14%(389/1488)、8.74%(130/1488);β地贫基因突变类型构成比前3位依次为β^(IVS-Ⅱ-654)/βN、βC^(D41-42)/β^(N)、β^(CD17)/β^(N),分别占41.72%(320/767)、21.25%(163/767)、16.04%(123/767);α地贫合并β地贫以-α^(3.7)/αα合并β^(IVS-Ⅱ-654)/βN和-α^(3.7)/αα合并β^(CD41-42)/β^(N)较为常见,分别占29.03%(9/31)、16.13%(5/31)。共对59例育龄人群进行产前诊断,其中,胎儿为重型地贫的有4例(重型α地贫2例、重型β地贫2例),中间型α地贫的有5例,中间型或重型β地贫的有5例,轻型地贫的有19例(轻型α地贫8例、轻型β地贫11例),静止型α地贫的有13例,静止型α地贫合并轻型β地贫的有1例,未携带α或β地贫基因的有12例。经随访,4例重型地贫、2例中间型α地贫、5例中间型或重型β地贫胎儿均由父母双方共同决定终止妊娠。结论湖北省育龄人群地贫检出率较高,突变类型以α地贫为主。育龄人群地贫基因筛查结合产前诊断对于降低地贫患儿的出生率具有重要意义。

Objective To study the genetic variation and distribution characteristics of thalassemia in people of childbearing age in Hubei Province,and to provide clinical basis for the local government decision-making departments to formulate and promote appropriate policies for prevention and control of thalassemia.Methods Venous blood samples were collected from 44849 people of childbearing age in hospitals in Hubei Province from May 13,2019 to August 17,2021.PCR-flow fluorescence hybridization and PCR+diversion hybridization were used to screen thalassemia genes.Spouses of those who tested positive were also tested for thalassemia genes.When both spouses carried the same type of thalassemia gene,the amniotic fluid of pregnant women was extracted for prenatal diagnosis and followed up.Results Among the 44849 people of childbearing age,2286 cases were diagnosed as thalassemia gene carriers through genetic testing,and the total detection rate was 5.10%(2286/44849).Among them,1488 cases were diagnosed asα-thalassemia,and the detection rate was 3.32%(1488/44849);767 cases were diagnosed asβ-thalassemia,and the detection rate was 1.71%(767/44849);31 cases were diagnosed asα-thalassemia combined withβ-thalassemia,and the detection rate was 0.07%(31/44849).The top three genotypes ofα-thalassemia were-α3.7/αα,--SEA/αα,and-α4.2/αα,accounting for 58.06%(864/1488),26.14%(389/1488),and8.74%(130/1488),respectively.The top three genotypes ofβ-thalassemia wereβ^(IVS-Ⅱ-654)/β^(N),βCD^(41-42)/β^(N),andβ^(CD17)/β^(N),accounting for 41.72%(320/767),21.25%(163/767),and 16.04%(123/767),respectively.The main genotypes ofα-thalassemia combined withβ-thalassemia were-α3.7/ααcomplexβ^(IVS-Ⅱ-654)/β^(N) and-α^(3.7)/ααcomplexβ^(CD41-42)/β^(N),accounting for 29.03%(9/31)and 16.13%(5/31),respectively.A total of 59 people of childbearing age were conducted prenatal diagnosis,among fetus,there were 4 cases of severe thalassemia(2 cases of severeα-thalassemia,2 cases of severeβ-thalassemia),5 cases of intermediateα-thalassemia,5 cases of intermediate or severeβ-thalassemia,19 cases of mild thalassemia(8 cases of mildα-thalassemia,11 cases of mildβ-thalassemia),13 cases of stationaryα-thalassemia,and 1 case of stationaryα-thalassemia combined with mildβ-thalassemia,there were 12 cases withoutα-thalassemia orβ-thalassemia genes.After follow-up,4 cases of severe thalassemia,2 cases of intermediateα-thalassemia,and 5 cases of intermediate or severeβ-thalassemia were terminated pregnancy by the joint decision of both parents.Conclusions In Hubei Province,the detection rate of thalassemia is high,andα-thalassemia is the main mutation type.The combination of thalassemia gene screening and prenatal diagnosis is of great significance in reducing the birth rate of children with thalassemia.