一个罕见的复合杂合子β地中海贫血家系的遗传学分析

Genetic Analysis of A Rare Family of Complex Heterozygotic Beta Thalassemia

通过对一罕见的复合杂合子β地中海贫血家系进行分析,探索其分子基础与临床表型的关系。先证者常规地中海贫血基因检测结果为IVS-Ⅱ-654(C>T)纯合子突变,血液学表型符合其基因型;先证者母亲常规地中海贫血基因型为β654M/βN,血液学表型符合其基因型;先证者哥哥常规地中海贫血基因型为βN/βN,血液学表型符合其基因型;先证者父亲常规地中海贫血基因型为βN/βN,血液学表型与基因型不相符。由于该家系基因结果不符合孟德尔遗传规律,进一步对先证者父亲及先证者进行了缺失型HPFH基因检测。综合常规地中海贫血基因检测和缺失型HPFH基因检测的结果,先证者父亲及先证者的地中海贫血基因型分别为βSEA-HPFH/βN和βSEA-HPFH/β654M。临床上仍然要重视β地中海贫血表型分析,当表型与基因型不一致时,需要重新检测或采用多种方法联合检测以避免假阴性的发生。

A rare family of complex heterozygotic beta thalassemia was analyzed to explore the relationship between its molecular basis and clinical phenotype.The results of routine genetic testing for thalassemia in the proband showed a homozygous mutation of IVS-Ⅱ-654(C>T),and her hematologic phenotype was consistent with this genotype.The conventional thalassemia genotype of the proband′s mother wasβ654M/βN,and the hematologic phenotype was consistent with her genotype.The conventional thalassemia genotype of the elder brother of the proband wasβN/βN,and the hematologic phenotype was consistent with his genotype.Notably,the conventional thalassemia genotype of the proband′s father wasβN/βN,while his hematologic phenotype did not match with the genotype.Since the genetic results of this family did not conform to the Mendelian inheritance rule,the gene detection of deletion HPFH was conducted additionally in the proband′s father and the proband.When the results of conventional thalassemia gene detection and deletion HPFH gene detection were combined,we found that the genotype of the proband′s father wasβSEA-HPFH/βN,and that the genotype of the proband wasβSEA-HPFH/β654M.Clinical attention should still be paid to the phenotypic analysis of beta thalassemia.When the phenotype and genotype are inconsistent,it is necessary to re-test or adopt multiple methods to avoid the false negative.