α2珠蛋白基因CD30(delGAG)突变的临床表型分析及产前基因诊断

Clinical phenotypic analysis and prenatal diagnosis of CD30(delGAG)onα2 hemoglobin gene

目的分析少见突变α2珠蛋白基因CD30(delGAG)病例的表型特征,并对携带此突变的家系进行产前基因诊断。方法采集所有病例外周血进行红细胞参数和血红蛋白电泳分析,收集羊水用于产前诊断。PCR-流式荧光杂交法和Sanger测序的方法被应用于珠蛋白基因突变检测。结果在5例CD30(delGAG)突变病例中,4例是此突变的杂合子,1例复合东南亚缺失型α地贫突变(--SEA/αCD30α)。所有杂合子均有小细胞低色素的血液学表现,但血红蛋白值均正常。--SEA/αCD30α病例除表现小细胞低色素特征以外,还有轻度贫血且血红蛋白电泳分析显示Hb H(35.8%)和Hb Bart’s(0.6%)明显升高。进行产前诊断的4个家系中,检测到1例胎儿为αCD30α/αα、2例胎儿为--SEA/αCD30α和1例胎儿为--SEA/-α4.2。结论α2珠蛋白基因CD30(delGAG)变杂合子携带者无贫血症状,复合其他α地中海贫血突变时会加重相关血液学表现。由于该突变不在临床地中海贫血常见基因突变类型检测范围内,因此应用其他分子方法精确诊断此突变对产前诊断具有重要价值。

Objective To analyze the clinical phenotypic characteristics of a rare mutation of CD30(delGAG)of HBA2 gene and performing prenatal diagnosis in these families.Methods Peripheral blood was collected for analysis of erythrocyte parameters and hemoglobin electrophoresis.Amniotic fluid was collected for prenatal diagnosis.PCR-flow fluorescence hybridization and Sanger sequencing were used to detect globin gene mutations.Results A total of five CD30(delGAG)mutations were found,including four heterozygotes and one compound heterozygote with common SEA deletionalα-thalassemia(-SEA/αCD30α).All heterozygotes had hematologic manifestations of small cell hypochromia,while hemoglobin values were normal.Patients with--SEA/αCD30αhad mild anemia and a significant reduction in erythrocyte parameters,as well as significant increase in Hb H(35.8%)and Hb Barts(0.6%)detected by hemoglobin electrophoresis.Among the four families in prenatal diagnosis,1 fetus withαCD30α/αα,2 fetuses with--SEA/αCD30α,and 1 fetus with--SEA/-α4.2 were detected.Conclusion Carriers of the CD30(delGAG)mutation of HBA2 gene have no anemia.However,the hematologic manifestations will be aggravated when associated with the same typeα-thalassemia.Since this mutation is not within the scope of routine clinical genetic testing for thalassemia,accurate diagnosis of this mutation by other molecular methods is of great value for prenatal diagnosis.