三代地贫检测方法检出的罕见HBA1基因突变复合中国型β缺失的地中海贫血的遗传学分析  

Identification of rare HBAl gene mutation and Chinese Gγ^(+)(Aγδβ)^(0)-thalassemia using third-generation sequencing in a family

作　　者：李金花[1] 赵文杰 何雨[2] 李丹花 覃茜[1] LI Jinhua;ZHAO Wenjie;HE Yu;LI Danhua;QIN Qian(Genetic Laboratory,Baise Maternal and Child Health Care Hospital,Baise,Guangxi 533000,China;Clinical Laboratory,The First Affiliated Hospital of Guangxi Medical University,Nanning,Guangxi 530021,China;Science and Technology Park of Changping District,Beijing 100010,China)

机构地区：[1]百色市妇幼保健院遗传实验室,广西百色533000 [2]广西医科大学第一附属医院检验科,广西南宁530021 [3]北京市昌平区科技园,北京100010

出　　处：《中国优生与遗传杂志》2024年第7期1464-1470,共7页Chinese Journal of Birth Health & Heredity

基　　金：百色市科学研究与技术开发计划课题(20220922)。

摘　　要：目的 通过分析三代地贫检测方法成功检出,而传统地贫基因检测方法未检出的血液学表型阳性的地中海贫血(地贫)病例家系样本,探讨三代地贫检测方法在地贫检测,特别是罕见地贫检测中的应用。方法 分别采用传统地贫基因检测方法(包含Gap-PCR法和PCR-RDB法)和三代地贫测序方法对疑似地贫的样本进行基因测序分析。结果 传统地贫基因检测方法未检出先证者及其父母样本的基因变异。通过三代地贫测序方法检出先证者和母亲均为HBA1基因c.300+55G>T突变与中国型Gγ^(+)(Aγδβ)^(0)缺失型地贫双重杂合子,先证者父亲相关基因没有变异。结论 通过三代地贫测序方法诊断出先证者及其母亲的αα/αα (HBA1:c.300+55G>T)和中国型Gγ^(+)(Aγδβ)^(0)/β^(N)的双重杂合子的罕见基因型,突显了三代地贫检测方法的优势,为三代地贫检测方法在地贫病例检出中的应用提供参考,也可以为罕见地贫病例的遗传咨询提供科学理论依据,对地贫携带者行出生缺陷干预,对优生优育具有重要的指导意义。Objective This study aims to explore the application of third-generation sequencing(TGS)for thalassemia variants detection,particularly rare variants,by analyzing family samples with positive hemetological phenotypes that had thalassemia variants identified by TGS but not by conventional methods.Methods The diagnosis of rare thalassemia was conducted using both third-generation sequencing and conventional methods including Gap-PCR and PCR-RDB.Results Conventional methods failed to detect any variants for genetic testing of thalassemia in the proband and his parents.In contrast,TGS successfully identified the HBAI gene c.300+55G>T variant and Chinese Gγ^(+)(Aγδβ)^(0)deletion in the proband and his mother.Conclusion The identification of the rare genotype,aa/aa(HBAl:c.300+55G>T)and Chinese Gγ^(+)(Aγδβ)^(0)/β^(N),provides a solid evidence for the advantage of third-generation sequencing used in thalassemia detection.This approach provides a theoretical basis for genetic counseling of rare thalassemia and can contribute to enhance birth defect intervention for severe thalassemia,promoting both antenatal and postnatal care.

关 键 词：地中海贫血 HBA1基因 中国型Gγ^(+)(Aγδβ)^(0)缺失地中海贫血 罕见地中海贫血检测 遗传学分析 

分 类 号：R556.61[医药卫生—血液循环系统疾病]