Mutation screening in binding motif of modifier sall2 gene in the beta thalassemia major patients

Objective: The aim of our thesis is to detect mutations in the domains and the SALL2 genetic binding motifs of modifying effect on chromatin remodeling and affecting HbF levels in beta thalassemia major patients(β-TM). Method: Our project was planned with 100 patients from Antalya Education and Research Hospital Adem Tolunay Thalassemia and Blood Disease Center, diagnosed with β-TM, defined as beta-globin gene mutations. Our project was carried out in a total of 76 patients; 10 and 66 of them have normal and high HbF, respectively. Following isolation of peripheral blood genomic DNA, gene regions related to the PCR method were amplified using primer pairs specific to the SALL2 gene binding motifs. Mutations were screened by Sanger Sequencing. The results were analyzed according to the NCBI database. Results: Of 76 patients with β-TM, 32 and 44 were males and females, respectively. The mean HbF levels of the patients as found to be 10.1 gr/dl. While in the second domain(2D) (D2), rs61746515 (C>T) g.18721G>A (Gly744=) was found as GG in 63(95.46%) patients and GA 3(4.54%) patients and rs1263810 (C>G) (g.18725C>G p.Gly746Arg) variations was found that this variation, g.18725C>G, as CC, CG and GG genotypes were found in 6(9,09%), 34(51,51%) and 26(39,39%) in the 66 patients. Mutations were not found in the first(D1) and third(D3) domains in the SALL2 gene, which worked as three PCR amplicons and modified HbF. Conclusion: We concluded that rs1263810 (C>G) variant (Gly746Arg) in the SALL2 gene binding motif detected by DNA sequencing for the first time in β-TM patients with high HbF in Turkish population may be important in the regulation of HbF and chromatin remodeling of SALL2. In the studies of HbF induction, SALL2 should be examined together with other transcription factors such as KLF1 and BCL11A. Key words: Thalassemia major, HbF, Modifier gene, SALL2