α2珠蛋白基因Questembert变异联合-α^(3.7)缺失导致α-地中海贫血一家系的遗传学研究  

Questembert variant with-α^(3.7) deletion of α2 globin gene detected in a alpha-thalassemia child and his family

作　　者：张鑫丽 阳鑫妙 唐克锋 李雯雯 沈国松 ZHANG Xinli;YANG Xinmiao;TANG Kefeng;LI Wenwen;SHEN Guosong(Department of Laboratory Medicine,Huzhou Maternity and Child Care Hospital,Huzhou 313000,China)

机构地区：[1]湖州市妇幼保健院医学检验中心,313000

出　　处：《浙江医学》2023年第23期2531-2534,共4页Zhejiang Medical Journal

基　　金：湖州市科技局计划项目(2023GY06)。

摘　　要：目的 对1例疑似α-地中海贫血患儿及其家系进行遗传学病因分析,了解基因型-表型关系,并进行产前诊断。方法 该疑似α-地中海贫血患儿(先证者)于2021年5月20日至湖州市妇幼保健院遗传咨询科就诊。收集该患儿及其家系成员的贫血相关资料,对先证者及其家系采用荧光定量PCR法对常见α-地中海贫血基因检测后,再进行先证者的血液系统疾病Panel二代测序,并利用Sanger测序法进行变异验证以及其家系成员和母亲羊水DNA的变异验证。结果 PCR法检出患儿-α^(3.7)缺失型变异,缺失来源于父亲;二代测序检测出先证者患有α2珠蛋白基因HbA2 c.394T>C(p.Ser132Pro)纯合变异,母亲和其家系检出多名该位点的杂合性变异,而母亲羊水DNA未检测到上述异常。结论 相较于αα/-α^(3.7)缺失,HbA2 c.394T>C杂合性非缺失型变异家系表现出更典型的α-地中海贫血特征。而HbA2基因的c.394T>C又称为Hb Questembert变异,为可疑致病性变异,丰富了中国人的α-地中海贫血致病基因变异谱,为该家系疾病的诊断、治疗和遗传咨询提供了依据。Objective To analyze the genotype of a suspected thalassemia child and his family.Methods A child with suspected thalassemia visited the Genetic Counseling department of Huzhou Maternity and Child Care Hospital on May 20th,2021.The blood samples were collected from the patient and her family members.The commonα-thalassemia genes were detected by fluorescence quantitative PCR,the blood system disease panel was detected by next generation sequencing,the results were verified by Sanger sequencing in the blood samples of the proband and his family members,as well as in the amniotic fluid DNA of his mother.Results Theαα/-α3.7 deletion was detected by PCR in blood samples of the proband and his father.The next generation sequencing showed that the proband had a α2-globin HbA2 c.394T(p.Ser 132Pro)homozygous variant in HbA2 gene,the heterozygous variation of this locus was also detected in the mother and his family,but not in the mother's amniotic fluid DNA.Conclusion A child with suspected thalassemia carrying HbA2 c.394T>C and-α^(3.7) deletion of α2 globin gene is reported in the study.Compared withαα/-α3.7 deletion carriers,those with HbA2 c.394T>C(Questembert variant)heterozygous variant may show more typical characteristics of thalassemia.

关 键 词：HbA2基因 Hb Questembert变异 -α^(3.7)缺失型变异 非缺失型变异 

分 类 号：R725.5[医药卫生—儿科]