144879名婚检、孕检者地中海贫血基因检测结果分析

Analysis on results of genetic testing for thalassemia in 144879 marriage and pregnancy tests

目的分析144879名婚检、孕检者的地中海贫血基因检测结果,为制定地中海贫血防治措施提供依据。方法以2017-2021年广西壮族自治区来宾市144879名参加免费婚检、孕检者为调查对象,采用血常规五分类法进行地中海贫血筛查,对地中海贫血基因携带者进行基因诊断,对因血液学表型与基因型不符样本进行罕见基因型检测。对妊娠者进行产前诊断,筛查中重度地中海贫血胎儿者。对地中海贫血筛查结果阳性者进行基因诊断,确定分型。采用描述性方法分析地中海贫血基因突变类型及罕见地中海贫血基因类型。结果筛查144879人,地中海贫血筛查结果阳性39444人,阳性检出率为27.23%(39444/144879)。784例β-地中海贫血基因阳性患者中,检出基因突变类型13种,以β^(CD41-42M)/β^(N)基因类型最多,占50.38%(395/784);β^(CD17M)/β^(N)基因类型次之,占38.08%(299/784);以上两种基因型占β-地中海贫血基因的88.52%(694/784)。202例αβ复合型地中海贫血基因阳性患者中,检出基因突变类型17种,以--^(SEA)/αα β^(CD41-42M)/β^(N)和-α3.7/αα β^(CD41-42M)/β^(N)两个基因突变类型最多,各36例。--^(SEA)/αα β^(CD41-42M)/β^(N)、-α3.7/αα β^(CD41-42M)/β^(N)、--^(SEA)/αα β^(CD17M)/β^(N)三个基因类型占αβ复合型地中海贫血基因的49.00%(99/202)。对282例因血液学表型与基因型不符样本进行罕见基因型检测,检出罕见地中海贫血基因突变52例,其中ɑ珠蛋白基因突变7种类型、β珠蛋白基因突变10种类型。而发生在ɑ2基因的IVS-Ⅱ-55(T->G)、IVS-Ⅱ-119(-G,+CTCGGCCC)及发生在β基因的CD81(C>A)、IVS-Ⅱ-672(A>C)尚未被人类异常血红蛋白地中海贫血库(HbVar)收录。检出一个新的地中海贫血突变基因型CD104(-A)。对地中海贫血基因诊断阳性的孕妇进行地中海贫血产前诊断,检出重型地中海贫血水肿胎儿263例,检出率为6.67‰(263/39444)。结论2017-2021年来宾市婚检、孕检人群的地中海贫血阳性检出率相对较高,而且变异基因类型复杂,罕见基因突变类型较多。此次筛查中检出一个新的地中海贫血突变基因型CD104(-A),补充了人类地中海贫血基因突变谱。

Objective To analyze the results of thalassemia genetic testing of 144879 marriage and pregnancy check-ups,so as to provide a basis for the development of thalassemia prevention and treatment measures.Methods The survey was based on 144879 people who participated in free marriage and pregnancy examinations in Laibin city,Guangxi Zhuang autonomous region from 2017 to 2021,and thalassemia screening was carried out using the five-classification method of blood counts,genetic diagnosis of thalassemia gene carriers,and testing of rare genotypes for samples that did not match genotypes due to hematological phenotypes.Prenatal diagnosis was performed on pregnant individuals to screen for thalassemia fetuses with moderate-to-severe thalassemia.Genetic diagnosis was performed to determine typing in those with positive thalassemia screening results.Descriptive methods were used to analyze the types of thalassemia gene mutations and rare thalassemia genotypes.Results Of the 144879 persons screened,39444 screened positive for thalassemia,a positive detection rate of 27.23%(39444/144879).Among the 784β-thalassemia gene-positive patients,13 mutation types were detected,with theβ^(CD41-42M)/β^(N) gene type being the most prevalent,accounting for 50.38%(395/784);followed by the β^(CD17M)/β^(N) gene type,which accounted for 38.08%(299/784);the above 2 genotypes accounted for 88.52% of the β-thalassemia gene(694/784).Among the 202αβ-complex thalassemia gene-positive patients,17 mutation types were detected,with--^(SEA)/αα β^(CD41-42M)/β^(N) and-α^(3.7)/αα β^(CD41-42M)/β^(N) being the 2 most frequent mutation types,with 36 cases each.The 3 gene types--^(SEA)/αα β^(CD41-42M)/β^(N),-α^(3.7)/αα β^(CD41-42M)/β^(N) and--^(SEA)/ααβ^(CD17M)/β^(N) accounted for 49.00%(99/202)of the genes for thalassemia of the αβ complex.Rare genotype testing was performed on 282 samples due to hematologic phenotypic and genotypic discrepancies,and 52 rare thalassemia gene mutations were detected,including 7 types ofɑ-globin gene mutations and 10 types of β-globin gene mutations.In contrast,IVS-II-55(T->G)and IVS-II-119(-G,+CTCGGCCC)occurring in the α2 gene and CD81(C>A)and IVS-II-672(A>C)occurring in the β gene have not yet been included in the Database of Human Hemoglobin Variants and Thalassemia mutations(HbVar).A new thalassemia mutant genotype CD104(-A)was detected.During prenatal diagnosis of thalassemia in pregnant women with a positive thalassemia gene diagnosis,263 fetuses with thalassemia major hydatidiform encephalopathy were detected,with a detection rate of 6.67‰(263/39444).Conclusion From 2017 to 2021,the incidence of thalassemia was relatively high in the premarital and pregnant population in Laibin city,and the variant gene types were complex,there were many rare gene mutation types,and a new mutant genotype was also found,which enriched the epidemiological data of thalassemia in the region and also supplemented the human thalassemia gene mutation spectrum.