~Aγ-225～-222缺失复合β地中海贫血的研究

RESEARCH ON THE ~Aγ-225 TO-222 DELETION IN COMPOUND WITHβ-THALASSEMIA

目的:探讨Aγ-225^-222缺失导致的非缺失型遗传性持续性胎儿血红蛋白综合征(nondeletional hereditary persistence of fetal hemoglobin,nd-HPFH)复合β地中海贫血的基因突变和临床特征。方法:选择2013年6月至2014年7月在广西医科大学第一附属医院就诊的病例进行血常规检查;应用高效液相色谱法(HPLC)测定血红蛋白Hb F和Hb A2水平;应用DNA测序方法分析γ珠蛋白基因突变;应用反向斑点杂交(RDB)和gap-PCR方法检测地中海贫血基因突变;应用SPSS 16.0统计软件对数据进行统计分析。结果:在122例Hb F增高的病例中,检测出7例Aγ-225^-222AGCA缺失杂合子,其中3例复合Gγ-158C→T突变杂合子,1例同时复合β地中海贫血-28A→G突变杂合子以及Gγ-158C→T突变杂合子,1例复合β地中海贫血CD17A→T突变杂合子。血常规检查显示7例Hb为96.7~142.3g/L,MCV为54.61~77.65fl,MCH为16.10~25.26pg。Hb分析显示7例Hb F为4.0%~11.2%,其中复合Gγ-158C→T突变杂合子Hb F为4.0%~8.1%,复合β地中海贫血杂合子Hb F为8.1%~11.2%。5例Hb A2正常,2例复合β地中海贫血杂合子Hb A2增高(5.6%~6.4%)。Aγ-225^-222缺失复合β地中海贫血杂合子与β地中海贫血杂合子相比,Hb F、Hb水平明显升高(P<0.05)。结论:Aγ-225^-222缺失可导致Hb F水平升高,其杂合子均无临床症状,Hb正常或降低,MCV、MCH降低。Aγ-225^-222缺失复合β地中海贫血杂合子的Hb F、Hb水平明显高于β地中海贫血杂合子。

Objective：To investigate the genotype and clinical features of the ^Aγ-225 to -222 deletion associated with non-deletional hereditary persistence of fetal hemoglobin （nd-HPFH） in compound with β-thalasse- mia. Methods：Cases admitted to the First Affiliated Hospital of Guangxi Medical University from June 2013 to July 2014 were subjects in this study. Hematological examination were performed. Hb F and Hb A2 were quantitated by high performance liquid chromatography （HPLC）. Genotypes were analyzed by DNA sequencing, reverse dot blot hybridization （RDB） and gap-polymerase chain reaction （gap-PCR）. The data were processed by SPSS 16.0 software. Results： 7 cases were identified as heterozygotes for the ^Aγ- 225 to -222 AGCA deletion among the 122 cases with elevated Hb F,while 3 cases in compound heterozy- gosity with ^Aγ-158 C→T mutation, 1 with β-thalassemia -28 A→G mutation and ^Gγ-158 C→T mutation, and 1 with β thalassemia CD17 A→T mutation. The hematological examination showed the Hb level from 96.7 to 142.3 g/L, MCV level from 54.61 to 77.65 fl and MCH level from 16.10 to 25.26 pg. Hemoglo-bin analysis showed the ^Aγ-225 to -222 deletion heterozygotes resulted in elevated Hb F level ranging from 4.0% to 11.2%, while the compound heterozy- gotes for the ^Aγ-225 to -222 deletion and the ^Aγ-158 C →T mutation showed Hb F level from 4.0% to 8.1%, and the compound heterozygotes for ^Aγ-225 to -222 deletion and β-thalassemia mutations showed Hb F level from 8.1% to 11.2%. The Hb A2 levels in 5 cases were normal, but were increased in 2 cases with β-thalassemia heterozygotes （ranging from 5.6% to 6.4%）. The compound heterozygotes for the ^Aγ-225 to -222 deletion and 13-thalassemia had higher Hb F and Hb levels than the β-thalassaemia heterozygotes （ P〈0.05）. Conclusion：The ^Aγ-225 to -222 deletion associated with nd-HPFH is probably responsible for the elevated Hb F. The heterozygotes all show no clinical symptoms, normal or lower Hb, lower MCV and MCH. The compound heterozygotes for the ^Aγ- 225 to -222 deletion and β-thalassemia were characterized by significantly elevated Hb F and Hb levels compared to the β-thalassaemia heterozygotes.