摘要目的 报告1例α地中海贫血(地贫)基因新型大片段缺失的患者,并对其家系进行分析,以提高对地贫发病机制及其诊断的认识.方法 采用血细胞分析和血红蛋白电泳进行地贫筛查,采用跨越缺口PCR(Gap-PCR)检测中国人常见的3种缺失型α地贫基因,采用PCR-寡核苷酸探针反向斑点杂交法检测中国人常见的3种非缺失型α地贫基因和17种β地贫基因点突变.对于常规地贫基因分析仍未能明确诊断的样本,采用多重连接探针扩增技术(MLPA)和DNA测序技术进行鉴定.结果 先证者表现为Hb H病,HGB 71 g/L、红细胞平均体积52.4 fl、红细胞平均血红蛋白含量16.1 pg、Hb A21.4％.常规地贫基因分析提示先证者α地贫基因大片段缺失.MLPA及DNA测序结果显示,该缺失片段长度为21 925 bp,为世界首次报道,命名为-α21.9,美国DNA数据库注册编号为KF360979.先证者及其胞妹基因型为--SEA/-α21.9,先证者母亲、父亲、胞弟基因型分别为αα-α21.9、--SEA/-α3.7及αα/-α3.7.结论 -α21.9缺失突变的发现,丰富了地贫基因突变数据库,对遗传咨询和地贫产前基因诊断具有重要意义.

abstractsObjective To raise awareness of the pathogenesis and diagnosis of thalassemia by reporting one case of α thalassemia patient with a large deletion fragment and analyzing the pedigree.Methods Firstly,blood cells and hemoglobin electrophoresis analysis were used for screening of thalassemia,and then three common kinds of deletional α thalassemia in Chinese was detected by Gap-PCR,three common kinds of non-deletional α thalassemia and seventeen common mutations of β thalassemia in Chinese were analyzed by using PCR-RDB.The unknown mutation of samples was identified with Multiplex Ligation-dependent Probe Amplification (MLPA) and DNA sequencing.Results The proband female presented with microcytic hypochromic anemia (hemoglobin 71g/L,mean corpuscular volume 52.4 fl,mean corpuscular hemoglobin 16.1 pg),and hemoglobin A2 1.4％.The identified large deletion fragment length was 21 925 bp,so far which had not been reported in the world and was named -α21.9.It was registered in USA DNA database and GenBank accession number as KF360979.The genotype of her mother and father and brother were αα/-α21.9,--SEA/-α3.7,αα/-α3.7 respectively,and the genotype of her and her sister were the same of--SEA/-α21.9.Her husband gene of thalassemia had no mutation,so prenatal diagnosis of thalassemia was not carried out in the pregnant woman.Conclusion The discovery of-α21.9 deletion mutation was enriched the DNA mutation gene database of thalassemia,and had important significance for genetic counseling and thalassemia prenatal diagnosis.