一种新的α2珠蛋白基因起始密码子变异联合右侧缺失型导致α-地中海贫血  

A case withα-thalassemia caused by novel start codon variant in conjunct with right deletion variant of α2-globin gene

作　　者：陈扬[1] 王洁[2] 王婵 陈仕平 冯女 刘海芳[1] 唐小燕 张淑芳[1] Chen Yang;Wang Jie;Wang Chan;Chen Shiping;Feng Nyu;Liu Haifang;Tang Xiaoyan;Zhang Shufang(Central Laboratory,the Affiliated Haikou Hospital of Xiangya Medical College,Central South University,Haikou,Hainan 570208,China;Neonatal Screening Center of Hainan Maternal and Child Health Care Hospital,Haikou,Hainan 570206,China;BGI Clinical Laboratory-Shenzhen,Shenzhen,Guangdong 518083,China)

机构地区：[1]中南大学湘雅医学院附属海口医院中心实验室,广东570208 [2]海南省妇幼保健院新生儿疾病筛查中心,海口570206 [3]深圳华大临床检验中心,广东518083

出　　处：《中华医学遗传学杂志》2021年第1期12-14,共3页Chinese Journal of Medical Genetics

基　　金：海南省卫生健康行业科研项目基金(20A200287);海南省重大科技项目(ZDKJ2017007);海南省医药卫生科研项目基金(18A200055);海口市人民医院院内课题(2017-YNK-20)。

摘　　要：目的对1例临床诊断为小细胞低色素性贫血、排除缺铁性贫血的先证者及其家系成员进行致病基因分析,了解基因型-表型关系。方法应用跨越断点PCR(Gap-PCR)和二代测序(next generation sequencing,NGS)技术检测先证者及家系成员在地中海贫血(简称地贫)缺失和变异型的情况,Sanger测序法对所检测的基因变异进行验证。结果Gap-PCR和NGS测序技术分别检测出α地贫αα/-α3.7缺失型和HBA2基因起始密码子HBA2 c.2T>A(p.Met1Lys)杂合变异,在先证者及父亲中均检出αHBA2:c.2T>A(p.Met1Lys)α/-α3.7,母亲及其他家系成员检出结果分别为-α3.7/-α3.7和αα/-α3.7。结论相较于只携带αα/-α3.7的α地贫静止型无症状家系成员,αHBA2 c.2T>A(p.Met1Lys)α/-α3.7表现出更典型的地贫体貌特征及异常血液学指标。HBA2 c.2T>A(p.Met1Lys)变异为致病性变异,新变异的检出丰富了α-地贫致病基因变异谱,为家系的遗传咨询和产前诊断提供了依据。Objective The explore the genetic basis for a patient with microcytic hypochromic anemia and iron deficiency anemia.Methods Common deletions and variants of the globin genes were detected by Gap-PCR and next generation sequencing(NGS).Suspected mutations were verified by Sanger sequencing.Results Gap-PCR and NGS showed that the proband has carried aαα/-α3.7 deletion and a heterozygous c.2T>A(p.Met1Lys)mutation in the initiation codon of the HBA2 gene.The patient and her father both carriedαHBA2 c.2T>A(p.Met1Lys)α/-α3.7,while her mother and other family members were-α3.7/-α3.7 andαα/-α3.7,respectively.Conclusion Patients withαHBA2c.2T>A(p.Met1Lys)α/-α3.7 genotype have typical features of thalassemia and abnormal hematologic indices compared with those withαα/-α3.7 genotype,suggesting that the HBA2 c.2T>A(p.Met1Lys)is a pathogenic variant.Above finding has enriched the spectrum ofα-thalassemia mutations and enabled genetic counseling and prenatal diagnosis for the family.

关 键 词：Α-珠蛋白 起始密码子变异 HBA2基因 右侧缺失型 

分 类 号：R556.61[医药卫生—血液循环系统疾病]