HBA2:c.2T>C和HBA2:c.2delT两例罕见突变引起血红蛋白H病家系分析  

Cases Analysis of Hemoglobin H Disease Caused by HBA2:c.2T>C and HBA2:c.2delT Mutations

作　　者：王秋华 陈杏园 唐宁 严提珍 黄钧 钟青燕 罗世强 WANG Qiu-Hua;CHEN Xing-Yuan;TANG Ning;YAN Ti-Zhen;HUANG Jun;ZHONG Qing-Yan;LUO Shi-Qiang(Department of Medical Genetics,Liuzhou Key Laboratory of Birth Defects Prevention and Control,Liuzhou Maternity and Child Healthcare Hospital,Liuzhou 545001,Guangxi Zhuang Autonomous Region,China;The People’s Hospital of Guangxi Zhuang Autonomous Region,Nanning 530000,Guangxi Zhuang Autonomous Region,China;The Reproductive Hospital of Guangxi Zhuang Autonomous Region,Nanning 530000,Guangxi Zhuang Autonomous Region,China)

机构地区：[1]柳州市妇幼保健院医学遗传科,广西柳州545001 [2]广西壮族自治区人民医院,广西南宁530000 [3]广西壮族自治区生殖医院,广西南宁530000

出　　处：《中国实验血液学杂志》2024年第2期520-524,共5页Journal of Experimental Hematology

基　　金：国家自然科学资金(81360091);柳州市科技重大专项项目(2018AF10501);广西壮族自治区卫生和计划生育委员会科研课题(Z20170528;Z-B20221578);柳州市科技创新能力和条件建设项目(2014G020404;2021YB0103A013);广西医学高层次骨干人才“139”计划培养目标专项(G202003028);柳州市科技计划项目(2022SB024)。

摘　　要：目的:分别对HBA2:c.2T>C和HBA2:c.2delT两种罕见HBA2基因起始密码子突变复合东南亚型α-地贫的血红蛋白H病病例及其家系成员进行致病基因分析,了解HBA2:c.2T>C和HBA2:c.2delT突变与临床表型的关系。方法:采集家系成员外周血进行血细胞分析及毛细管电泳血红蛋白分析,缺口PCR(Gap-PCR)、反向点杂交法(RDB)检测ɑ-地贫基因常见类型突变,Sanger测序法对HBA1和HBA2基因序列进行分析。结果:检测出两个先证者基因型分别为--SEA/αα复合HBA2:c.2T>C和--SEA/αα复合HBA2:c.2delT,家系成员中检出HBA2:c.2T>C/WT和HBA2:c.2delT/WT,均表现为小细胞低色素性贫血。结论:HBA2:c.2T>C和HBA2:c.2delT为杂合突变时机体可出现静止型α-地贫的表型,当其复合轻型α-地贫时可使机体出现血红蛋白H病的临床表现,本研究为遗传咨询提供依据。Objective:To investigate two cases of rare pathogenic genes,initiation codon mutations in HBA2 gene,combined with Southeast Asian deletion and their family members to understand the relationship of HBA2:c.2T>C and HBA2:c.2delT mutations with clinical phenotype.Methods:The peripheral blood of family members was obtained for blood cell analysis and capillary electrophoresis hemoglobin analysis.Gap-PCR and reverse dot blotting(RDB)were used to detect common types of mutations inɑ-thalassaemia gene.Sanger sequencing was used to analyze HBA1 and HBA2 gene sequence.Results:Two proband genotypes were identified as--SEA/ααwith HBA2:c.2T>C and--SEA/ααwith HBA2:c.2delT.HBA2:c.2T>C/WT and HBA2:c.2delT/WT was detected in family members.They all presented with microcytic hypochromic anemia.Conclusion:When HBA2:c.2T>C and HBA2:c.2delT are heterozygous that can lead to staticα-thalassemia phenotype,and when combined with mildα-thalassemia,they can lead to the clinical manifestations of hemoglobin H disease.This study provides a basis for genetic counseling.

关 键 词：α-珠蛋白基因 HBA2:c.2T>C HBA2:c.2delT 血红蛋白H病 

分 类 号：R556.61[医药卫生—血液循环系统疾病]