成都地区0~18岁地中海贫血患儿的基因突变类型及频率分析

Analysis of gene mutation type and frequency in children with thalassemia aged 0-18 years in Chengdu,Sichuan

目的分析成都地区0~18岁患儿地中海贫血基因突变类型及频率。方法选取2018年9月至2021年7月在成都市及周边地区接诊的贫血患儿中地中海贫血初筛阳性的568例患儿,其中男308例,女260例。采用PCR-反向点杂交法,分析纳入研究患儿的α、β各型地中海贫血的基因突变类型及分布等。结果568例初筛阳性地中海贫血的患儿中,基因检出地中海贫血356例,总阳性率为62.68%,其中α地中海贫血140例,阳性率为24.65%,β地中海贫血202例,阳性率为35.56%,α复合β地中海贫血基因携带者14例,阳性率为2.46%。α地中海贫血基因突变类型以αα/--sea(79.29%,111/140)、α/-α3(7.86%,11/140)、-α3.7/--sea(7.14%,10/140)基因型较多,占全部类型的94.29%;在202例β地中海贫血患儿中,单纯杂合子199例,以cd17(A➝T)(36.13%,73/202)、cd41-42(-TCTT)(32.68%,64/202)、IVS-2-654(C➝T)(20.79%,42/202)基因型较多,占全部基因突变类型的88.61%(179/202),β-地中海贫血双重杂合子3例(1.48%,3/202),未检出β地中海贫血纯合子;α复合β地中海贫血占14例,其中cd41-42(-TCTT)/-α3.7、VS-2-654(C➝T)/--sea、cd17(A➝T)/-α3.7、cd41-42(-TCTT)/--sea各2例。男性、女性患α、β地中海贫血差异无统计学意义(P>0.05),但α复合β地中海贫血则以男性较多(13/14比1/14,χ^(2)=8.532,P=0.003)。结论成都地区α地中海贫血基因突变以αα/--sea为主,β地中海贫血以cd17(A➝T)突变多见,男性的α复合β地中海贫血较常见,为成都地区制定地中海贫血防治策略提供参考依据。

Objective To analyze the type and frequency of thalassemia gene mutation in children aged 0 to 18 years in Chengdu.Methods A total of 568 children from Chengdu,who were initially positive for thalassemia during screening from September 2018 to July 2021,were recruited.Among them,there were 308 males and 260 females.The type of mutation and distribution of α and β types of thalassemia in this cohort was analyzed utilizing PCR reverse dot blot.Results Among the 568 children,356 were genetically diagnosed as thalassemia,with a total positive rate of 62.68%.Among them,there were 140 cases of α-thalassemia with a positive rate of 24.65%,and 202 cases of β-thalassemia with a positive rate of 35.56%.There were 14 carriers of α-complex β-thalassemia gene,and the positive rate was 2.46%.Among these cases,the types of α-thalassemia gene mutation were mainly αα/--sea(79.29%),αα/-α3.7(7.86%),and-α3.7/--sea(7.14%)genotypes,accounting for 94.29% of all types.In the 202 β-thalassemia patients,199 heterozygous mutations were identified,mainly including cd17(A➝T)(36.13%),cd41-42(-TCTT)(32.68%),IVS-2-654(C➝T)(20.79%),and accounting for 88.61%of all types of gene mutation,and 3 compound heterozygous mutations were detected.α-complex β-thalassemia was detected in 14 patients,including cd41-42(-TCTT)/-α3.7,VS-2-654(C➝T)/--sea,cd17(A➝T)/-α3.7 and cd41-42(-TCTT)/--sea,which accounting for 57.14% of all types of gene mutation.Our results showed that there is no sex difference betweenαandβthalassemia in Chengdu area,whereas the prevalence ofαcombined with β thalassemia is higher in males(P=0.003).Conclusions The type of α-thalassemia mutation in Chengdu is mainly αα/--sea,whereas β-thalassemia with cd17(A➝T)mutations andα-complex β-thalassemia are more frequent in males.This study provides a reference for the formulation of prevention and control strategies for thalassemia in Chengdu.