title: Known and new hemoglobin A2 variants in Thailand and implication for β-thalassemia screening.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  Hb analysis revealed Hb A2 variant in all cases. DNA analysis of δ-globin gene identified the Hb A2-Melbourne [δ43(CD2)Glu→Lys] 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)GAT→AAT; Asp→Asn] found in association with Hb E and α(+)-thalassemia. These mutations could be identified using PCR-RFLP and allele specific PCR assays developed.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Biomedical Science Program, Graduate School, Khon Kaen University, Thailand; Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Sitthichai
authors.initials: S
authors.lastname: Panyasai
authors.affiliation: Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Goonnapa
authors.initials: G
authors.lastname: Fucharoen
authors.affiliation: Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand. Electronic address: supan@kku.ac.th.
authors.forename: Supan
authors.initials: S
authors.lastname: Fucharoen
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D005260:Female; D006443:Hemoglobin A2 / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006456:Hemoglobinuria / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D013785:Thailand; D017086:beta-Thalassemia / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D006455:Hemoglobins, Abnormal; D006443:Hemoglobin A2
keywords: Hb A(2)-Lampang; Hb A(2)-Melbourne; Hb A(2)-variants; Thalassemia screening