异常血红蛋白Hb Rush复合β0地中海贫血的一个重型地贫家系分析  

Compound heterozygosity for unstable Hb Rush and beta(0)-thalassemia found in a family with severe anemia

作　　者：番云华 葛世军 罗赛丽 禹崇飞 易薇 杨必清 褚嘉祐[2] 杨昭庆[2] FAN Yunhua;GE Shijun;LUO Saili;YU Chongfei;YI Wei;YANG Biqing;CHU Jiayou;YANG Zhaoqing(Clinical Laboratory,People's Hospital of Dehong Prefecture,Mangshi,Yunnan 678400,China;Medical Genetics Department,Institute of Medical Biology,Chinese Academy of Medical Sciences&Peking Union Medical College,Kunming,Yunnan 650118,China)

机构地区：[1]德宏州人民医院检验科,云南芒市678400 [2]中国医学科学院&北京协和医学院医学生物学研究所医学遗传学研究室,云南昆明650118

出　　处：《中国优生与遗传杂志》2024年第4期786-789,共4页Chinese Journal of Birth Health & Heredity

基　　金：云南省基础研究计划(202101AY070001-230);云南省医学领军人才培养计划(L-2018003);云南省重点研发计划(202103AF140002)。

摘　　要：目的对同时携带有异常血红蛋白Hb Rush和β^(0)地中海贫血β^(CD71-72)突变的家系进行基因诊断,并探讨Hb Rush/β^(CD71-72)复合杂合子的临床血液学特征。方法采用血常规和血红蛋白电泳分析家系成员的血液学指标,采用PCR-流式杂交法和基因测序方法进行基因诊断。结果该家系中先证者血液学表型为重度贫血,显著的小细胞低色素,血红蛋白电泳无HbA,出现异常的Z8区条带和明显增高的HbF。基因测序结果证实为不稳定异常血红蛋白Hb Rush复合β^(CD71-72)地中海贫血。家系中携带相同复合突变的成员临床血液表型与先证者相似,仅携带异常血红蛋白Hb Rush突变的无明显贫血,β^(CD71-72)杂合子的家庭成员表现为轻微的小细胞低色素表型。结论异常血红蛋白Hb Rush杂合子无明显贫血临床表型,但复合β^(0)地中海贫血时可表现出重型地中海贫血临床表型特征。本研究为异常血红蛋白病与地中海贫血的相互作用提供了新的基因型-表型关联性数据,为遗传性血液病的临床诊断和遗传咨询提供了更多参考依据。Objective To carry out genetic diagnosis in a family coinherited with both hemoglobin variant Hb Rush and beta(0)-thalassemia,and to explore the clinical hematological characteristics of a compound heterozygous status with Hb Rush and beta-thalassemia CD71-72.Methods Hematological indicators of the families were obtained by using routine blood tests and hemoglobin electrophoresis,and PCR-flow hybridization and gene sequencing were used for genetic diagnosis.Results The proband presented severe microcytic hypochromia anemia with absent HbA,abnormal Z8 band,and significantly increased HbF.Compound heterozygotes of Hb Rush and beta(0)thalassemia CD71-72 were confirmed in the family.The clinical phenotypes of the family members with the same compound mutation were similar to that of the proband,while the family members who only carry either abnormal hemoglobin Hb Rush or beta-thalassemia CD71-72 heterozygous were asymptomatic or mild anemia.Conclusion Unstable hemoglobin Hb Rush trait usually is asymptomatic,however it co-inheriting with beta(0)-thalassemia can lead to thalassemia major with severe anemia.Our study provides more clinical and genetic details on genotype-phenotype correlation for compound heterozygous status with unstable hemoglobin variant and thalassemia,which provides more references for clinical diagnosis and genetic counseling of hemoglobin disorders.

关 键 词：异常血红蛋白 Hb Rush 地中海贫血 基因突变 基因诊断 

分 类 号：R556.61[医药卫生—血液循环系统疾病]