Hb Lepore-Boston-Washington型杂合缺失的诊断分析及文献复习  

Diagnostic Analysis of Hb Lepore-Boston-Washington and Literature Review

作　　者：唐斌[1] 王继成[1] 秦丹卿[1] 姚翠泽 梁杰 梁凯玲 陈柯艺 詹文丽 梁丽华 柴慧颖 郭浩[1] 杜丽[1] Tang Bin;Wang Jicheng;Qin Danqing;Yao Cuize;Liang Jie;Liang Kailing;Cheng Keyi;Zhan Wenli;Liang Lihua;Chai Huiying;Guo Hao;Du Li(Department of Medical Genetics Center,Guangdong Women and Children Hospital,Guangzhou 511400,Guangdong,China)

机构地区：[1]广东省妇幼保健院医学遗传中心,广东广州511400

出　　处：《中国产前诊断杂志（电子版）》2024年第2期25-30,共6页Chinese Journal of Prenatal Diagnosis(Electronic Version)

基　　金：广州科技计划项目(202002030390)。

摘　　要：目的报道国内罕见的Hb Lepore-Boston-Washington杂合缺失病例并探讨毛细管电泳法和高效液相色谱法对其筛查时需要注意的问题,结合文献探讨该病的血液学特点和临床表型,以期为临床诊疗提供参考。方法采集外周血进行血液学分析。采用全自动毛细管电泳系统检测血红蛋白组分。应用PCR-流式荧光杂交法对常见的α-珠蛋白基因3种缺失、3种突变、β-珠蛋白基因17种突变进行检测。应用DNA测序分析HBB突变类型。结果该患者血液学表型为HGB:136 g/L、RBC:5.8×10^(12)/L、MCV:71.4 fL、MCH:23.4 pg。毛细管电泳结果显示:Hb A:84.7%;Hb A_(2):2.3%;Hb F:2.9%;Hb D:10.1%。DNA测序结果显示为Hb Lepore-Boston-Washington型杂合缺失。结论该病例为β珠蛋白基因第二内含子基因序列与δ珠蛋白基因序列发生了融合,不等交换重组位点发生在δ-基因87位与β-基因IVS-II nt 8之间。该类型突变在中国人群中属于罕见型,确诊需要依赖基因诊断。在地中海贫血(地贫)高危人群中,尤其是当其配偶疑似为β-地贫携带者时,要警惕此类地贫基因突变的筛查和检测,避免重型β-地贫患儿的出生。Objective In order to provide reference for clinic, this paper reports a rare heterozygote Hb Lepore-Boston-Washington(Hb LBW) in China and pay attention to detail(inspection of the capillary zone electrophoresis system and HPLC chromatogram in this case) and awareness of strengths and pitfalls of each screening technique. Hematological characteristics and clinical phenotype were discussed and compared with cases in previous literatures. Methods Peripheral blood was collected for hematological analysis. Three common deletion a-thalassaemia(-α^(3.7),-α^(4.2),--^(SEA)), three common non-deletion a-thalassaemia(Hb Constant Spring, Hb QuongSze and Hb Westmead) and 17 common mutations were analyzed by PCR-flow fluorescence hybridization, and DNA sequencing was used to analyzed β-globin gene.Results His haematology profile showed a Hb of level 136 g/L, RBC:5.8×10^(12)/L, MCV: 71.4 fl and MCH: 23.4 pg. On the capillary zone electrophoresis, the results of Hb typing showed that the contents of Hb A, Hb A_(2), Hb F and Hb D were 84.7%, 2.3%, 2.9% and 10.1%, respectively. DNA analysis revealed the patient was a rare heterozygote Hb Lepore-Boston-Washington carrier. Conclusion This rare Hb LBW mutation in the Chinese population could explain variant Hb peak and raised Hb F level resulting from unequal crossover events occur between the homologous regions of the δ-codon 88 to β-IVS-II nt 8 that would form a fusion gene. An accurate diagnosis could be reached with the help of DNA analysis. In areas where thalassemia has a relatively high prevalence in southern Chinese population, extreme attention is necessary for couples who seek for preconception genetic consultation, especially when one partner has been identified to have β-thal trait.

关 键 词：Hb Lepore-Boston-Washington δ珠蛋白 Β珠蛋白 基因重组 罕见型 

分 类 号：R715.5[医药卫生—妇产科学]