title: Molecular Understanding of Non-Transfusion-Dependent Thalassemia Associated with Hemoglobin E-β-Thalassemia in Northeast Thailand.
abstract: Non-transfusion-dependent thalassemia (NTDT) is associated with various forms of thalassemia and genetic modifiers. We report the molecular basis of NTDT in hemoglobin (Hb) E-β-thalassemia disease. This study was done in 73 adult patients encountered at the prenatal diagnosis center of Khon Kaen University, Northeast Thailand. Hematological parameters and Hb patterns were collected, and α- and β-globin gene mutations were determined. Multiple single-nucleotide polymorphisms (SNPs) including the rs7482144/Gγ-XmnI polymorphism, rs2297339, rs2838513, rs4895441, and rs9399137 in the HBS1L-MYB gene, rs4671393 and rs11886868 in the BCL11A gene, and G176AfsX179 in the KLF1 gene were examined. Five β0-thalassemia mutations and a severe β+-thalassemia mutation in trans to the βE gene were identified. No significant difference in hematological parameters was observed among β-thalassemia genotypes. Coinheritance of α-thalassemia was observed in 31 of the 73 subjects (42.5%). Four SNPs including Gγ-XmnI, rs2297339, rs4895441, and rs9399137 of HBS1L-MYB were found to be associated with high Hb F levels in 39 (53.4%) subjects. The molecular basis of NTDT in the remaining 3 (4.1%) cases could not be defined. These results indicate multiple genetic factors in NTDT patients and underline the importance of complete genotyping to provide proper management, make clinical predictions, and improve genetic counseling.
authors.affiliation: Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Supawadee
authors.initials: S
authors.lastname: Yamsri
authors.forename: Naruwat
authors.initials: N
authors.lastname: Pakdee
authors.forename: Goonnapa
authors.initials: G
authors.lastname: Fucharoen
authors.forename: Kanokwan
authors.initials: K
authors.lastname: Sanchaisuriya
authors.forename: Supan
authors.initials: S
authors.lastname: Fucharoen
mesh_terms: D002352:Carrier Proteins / Q000235:genetics; D005260:Female; D005838:Genotype; D006446:Hemoglobin E; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D020626:Oncogene Proteins v-myb / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012097:Repressor Proteins; D013785:Thailand / Q000453:epidemiology; D055542:alpha-Globins / Q000235:genetics; D055544:beta-Globins / Q000235:genetics; D017086:beta-Thalassemia / Q000453:epidemiology / Q000235:genetics*
chemical_list: C486563:BCL11A protein, human; D002352:Carrier Proteins; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D020626:Oncogene Proteins v-myb; D012097:Repressor Proteins; D055542:alpha-Globins; D055544:beta-Globins; C080774:erythroid Kruppel-like factor; D006446:Hemoglobin E