一种新的α2珠蛋白基因起始密码子变异联合右侧缺失型导致α-地中海贫血

A case withα-thalassemia caused by novel start codon variant in conjunct with right deletion variant of α2-globin gene

目的对1例临床诊断为小细胞低色素性贫血、排除缺铁性贫血的先证者及其家系成员进行致病基因分析,了解基因型-表型关系。方法应用跨越断点PCR(Gap-PCR)和二代测序(next generation sequencing,NGS)技术检测先证者及家系成员在地中海贫血(简称地贫)缺失和变异型的情况,Sanger测序法对所检测的基因变异进行验证。结果Gap-PCR和NGS测序技术分别检测出α地贫αα/-α3.7缺失型和HBA2基因起始密码子HBA2 c.2T>A(p.Met1Lys)杂合变异,在先证者及父亲中均检出αHBA2:c.2T>A(p.Met1Lys)α/-α3.7,母亲及其他家系成员检出结果分别为-α3.7/-α3.7和αα/-α3.7。结论相较于只携带αα/-α3.7的α地贫静止型无症状家系成员,αHBA2 c.2T>A(p.Met1Lys)α/-α3.7表现出更典型的地贫体貌特征及异常血液学指标。HBA2 c.2T>A(p.Met1Lys)变异为致病性变异,新变异的检出丰富了α-地贫致病基因变异谱,为家系的遗传咨询和产前诊断提供了依据。

Objective The explore the genetic basis for a patient with microcytic hypochromic anemia and iron deficiency anemia.Methods Common deletions and variants of the globin genes were detected by Gap-PCR and next generation sequencing(NGS).Suspected mutations were verified by Sanger sequencing.Results Gap-PCR and NGS showed that the proband has carried aαα/-α3.7 deletion and a heterozygous c.2T>A(p.Met1Lys)mutation in the initiation codon of the HBA2 gene.The patient and her father both carriedαHBA2 c.2T>A(p.Met1Lys)α/-α3.7,while her mother and other family members were-α3.7/-α3.7 andαα/-α3.7,respectively.Conclusion Patients withαHBA2c.2T>A(p.Met1Lys)α/-α3.7 genotype have typical features of thalassemia and abnormal hematologic indices compared with those withαα/-α3.7 genotype,suggesting that the HBA2 c.2T>A(p.Met1Lys)is a pathogenic variant.Above finding has enriched the spectrum ofα-thalassemia mutations and enabled genetic counseling and prenatal diagnosis for the family.