摘要
目的探讨贵阳及周边地区罕见珠蛋白基因突变类型及分布情况,为血红蛋白病的基因诊断及遗传咨询提供参考依据。方法收集地中海贫血基因检测的人群样本5574例,筛选出符合条件的588例全血样本,运用跨越断裂位点PCR(Gap-polymerase chain reaction,Gap-PCR)检测缺失型突变、采用双脱氧链终止(Sanger测序)法进行基因序列测定,分析受检者是否携带罕见珠蛋白基因突变类型。结果在588例标本中,共检出罕见珠蛋白基因突变97例,阳性率为16.50%(97/588),主要为α和β珠蛋白基因突变,分别占27.83%(27/97)和50.52%(49/97),γ珠蛋白基因突变9例,δ珠蛋白基因突变2例,复合型突变10例;97例突变中基因型共50种,其中IVS-II-462(C>T)inβ,IVS-II-676(A>C)inβ,IVS-II-820(C>T)inβ,Codon112(-C)inα2,Codon125(CTG>TTG)inα2,IVS-I-60(C>T)inα1,NG_000007.3:g.64760(T>C)inδ,-314(G>T)in Aγ为新发现的基因突变类型。结论对于血液学筛查结果与基因检测结果不符,或表型与基因型不一致的受检者,建议进一步开展罕见珠蛋白基因突变检测,以明确其基因型,这不仅有助于降低血红蛋白病的漏检率,还可为预防出生缺陷、遗传咨询以及产前诊断等提供科学依据。
Objective To investigate the types and distribution of rare globin gene mutations in Guiyang and the surrounding regions and support a reference foundation for the genetic diagnosis and counseling of hemoglobinopathies.Methods A total of 5574 individuals who underwent thalassemia gene testing were included in this study.Among them,588 whole blood samples meeting the inclusion criteria were selected for further analysis.Gap-PCR and Sanger sequencing methods were employed to identify rare globin gene mutations carried by these subjects.Results Among the 588 specimens analyzed,97 rare globin gene mutations were identified with a positive detection rate of 16.50%.Of these mutations,27.83%(27/97)occurred in theα-globin gene and 50.52%(49/97)in theβ-globin gene.Additionally,9γ-globin gene mutations,2δ-globin gene mutations,and 10 compound mutations were detected.Among the 97 mutations,55 distinct genotypes were observed,including 8 newly identified mutations:IVS-II-462(C>T)inβ,IVS-II-676(A>C)inβ,IVS-II-820(C>T)inβ,Codon112(-C)inα2,Codon125(CTG>TTG)inα2,IVS-I-60(C>T)inα1,NG_000007.3:g.64760(T>C)inδ,and-314(G>T)in Aγ.Conclusion For individuals with discrepant hematology screening and genetic test results,or those exhibiting phenotypic-genotypic inconsistencies,further rare globin gene mutation analysis is recommended to accurately determine their genotypes.This approach can not only reduce the risk of missed hemoglobinopathy diagnoses but also provide a robust scientific foundation for birth defect prevention,genetic counseling,and prenatal diagnosis.
作者
王侣金
兰冰雪
杨雪
张禾璇
汤贤英
夏开德
金平
张琳琳
黄海
WANG Lvjin;LAN Bingxue;YANG Xue;ZHANG Hexuan;TANG Xianying;XIA Kaide;JIN Ping;ZHANG Linlin;HUANG Hai(Clinical Laboratory Center,the Affiliated Hospital of Guizhou Medical University,Guiyang 550004,Guizhou,China;Department of Prenatal Diagnosis and Genetic Counseling,Guiyang Maternal and Child Health Care Hospital,Guiyang 550000,Guizhou,China)
出处
《贵州医科大学学报》
2025年第8期1220-1229,共10页
Journal of Guizhou Medical University
基金
贵州省卫生健康委科学技术基金项目(gzwkj2024-313)。
关键词
罕见
珠蛋白
基因突变
漏检
遗传咨询
rare
globin
gene mutation
missed detection
genetic counseling
