Molecular Understanding of Non-Transfusion-Dependent Thalassemia Associated with Hemoglobin E-beta-Thalassemia in Northeast Thailand

作者：Yamsri Supawadee; Pakdee Naruwat; Fucharoen Goonnapa; Sanchaisuriya Kanokwan; Fucharoen Supan^*

来源：Acta Haematologica, 2016, 136(4): 233-239.

DOI：10.1159/000449120

• BCL11A
• HBS1L-MYB
• Hemoglobin E-beta-thalassemia
• Hemoglobin F expression
• KLF1
• Non-transfusion-dependent thalassemia

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-beta-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 a-and beta-globin gene mutations were determined. Multiple single-nucleotide polymorphisms (SNPs) including the rs7482144/(G)gamma-Xmnl 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 beta(0)-thalassemia mutations and a severe beta(+)-thalassemia mutation in trans to the beta(E) gene were identified. No significant difference in hematological parameters was observed among beta-thalassemia genotypes. Coinheritance of alpha-thalassemia was observed in 31 of the 73 subjects (42.5%). Four SNPs including (G)gamma-Xmnl, 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.

• 出版日期2016