Abstract:

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 was β^654M/β^N, and the hematologic phenotype was consistent with her genotype. The conventional thalassemia genotype of the elder brother of the proband was β^N/β^N, and the hematologic phenotype was consistent with his genotype. Notably, the conventional thalassemia genotype of the proband′s father was β^N/β^N, 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 was β^SEA-HPFH/β^N, and that the genotype of the proband was β^SEA-HPFH/β^654M. 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.

Key words: Beta-thalassemia, Genetic testing, Genotype, Hematology, Hemoglobinometry, Heterozygote, Phenotype