Objective: To investigate two cases of rare pathogenic genes, initiation codon mutations in HBA2 gene, combined with Southeast Asian deletion and their family members to understand the relationship of HBA2:c.2T>C and HBA2:c.2delT mutations with clinical phenotype.
Methods: The peripheral blood of family members was obtained for blood cell analysis and capillary electrophoresis hemoglobin analysis. Gap-PCR and reverse dot blotting (RDB) were used to detect common types of mutations in ɑ-thalassaemia gene. Sanger sequencing was used to analyze HBA1 and HBA2 gene sequence.
Results: Two proband genotypes were identified as --SEA/αα with HBA2:c.2T>C and --SEA/αα with HBA2:c.2delT. HBA2:c.2T>C/WT and HBA2:c.2delT/WT was detected in family members. They all presented with microcytic hypochromic anemia.
Conclusion: When HBA2:c.2T>C and HBA2:c.2delT are heterozygous that can lead to static α-thalassemia phenotype, and when combined with mild α-thalassemia, they can lead to the clinical manifestations of hemoglobin H disease. This study provides a basis for genetic counseling.
题目: HBA2:c.2T>C 和HBA2:c.2delT两例罕见突变引起血红蛋白H病家系分析.
目的: 分别对HBA2:c.2T>C 和HBA2:c.2delT 两种罕见HBA2 基因起始密码子突变复合东南亚型α-地贫的血红蛋白H病病例及其家系成员进行致病基因分析，了解HBA2:c.2T>C 和HBA2:c.2delT 突变与临床表型的关系。.
方法: 采集家系成员外周血进行血细胞分析及毛细管电泳血红蛋白分析，缺口PCR（Gap-PCR）、反向点杂交法（RDB）检测ɑ-地贫基因常见类型突变，Sanger测序法对HBA1 和HBA2 基因序列进行分析。.
结果: 检测出两个先证者基因型分别为--SEA/αα复合HBA2:c.2T>C 和--SEA/αα复合HBA2:c.2delT ，家系成员中检出HBA2:c.2T>C/WT 和HBA2:c.2delT/WT ，均表现为小细胞低色素性贫血。.
结论: HBA2:c.2T>C和HBA2:c.2delT 为杂合突变时机体可出现静止型α-地贫的表型，当其复合轻型α-地贫时可使机体出现血红蛋白H病的临床表现，本研究为遗传咨询提供依据。.
Keywords: α-globin gene; HBA2: c.2T>C; HBA2: c.2delT; hemoglobin H disease.