Molecular genetic diagnosis of a carrier with rare α-thalassemia mutations / 中华医学遗传学杂志

ABSTRACT

OBJECTIVE@#To explore the cause of inconsistent genotypes for an α-thalassemia carrier by using two commercial genotyping kits.@*METHODS@#GAP-PCR and PCR-reverse dot blotting (PCR-RDB) were employed to determine the genotype of the carrier, while Sanger sequencing was used to verify the results.@*RESULTS@#Sequencing analysis demonstrated that the subject has carried a α1 globin gene with a 3.7 kb heterozygous deletion. In addition, two novel mutations, IVS-II-55(T>G) and IVS-II-119(G>TCGGCCC), were found in intron 2 of α2 globin gene.@*CONCLUSION@#The two mutations located in the binding regions of PCR primers have caused failure of PCR amplification and misreading of the genotype. Combination of clinical and hematological phenotypes is indispensible to infer the genotype of carriers for accurate diagnosis.