Rare Diseases Symptoms Automatic Extraction

Known and new hemoglobin A2 variants in Thailand and implication for β-thalassemia screening.


We reported molecular and hematological characteristics of δ-globin chain variants and addressed diagnostic consideration of complex hemoglobinopathies caused by their interactions with α- and β-thalassemias.Study was done on four unrelated Thai subjects with second Hb A2 fractions. Hb analysis was carried out using automated HPLC and capillary electrophoresis. Mutations were identified by DNA analysis. Novel diagnostic methods based on PCR-RFLP and allele specific PCR were developed.Hb analysis revealed Hb A2 variant in all cases. DNA analysis of δ-globin gene identified the Hb A2-Melbourne [δ43(CD2)GluLys] in combination with α(+)-thalassemia, α(0)-thalassemia and β(0)-thalassemia in the first three cases, respectively. Analysis of the remaining case identified a novel δ-Hb variant namely the Hb A2-Lampang [δ47(CD6)GATAAT; AspAsn] found in association with Hb E and α(+)-thalassemia. These mutations could be identified using PCR-RFLP and allele specific PCR assays developed.It is necessary to recognize the Hb A2 variant and to combine the amounts of Hb A2 and Hb A2-variant for a total Hb A2 value to make better diagnostic of these complex syndromes. Co-inheritance of these multiple globin gene defects could lead to complex hemoglobinopathies requiring comprehensive Hb and molecular assessments.