Mutation analysis of alpha thalassemia trait in children livig in Aydin and peripheric regions

OBJECTIVE To determine the type of mutation in the children who have been diagnosed as α thalassemia carriers living in Aydin and its peripheric regions and to evaluate the effect of this mutations on haematologic parameters. MATERIALS AND METHODS Fifty two patients who have been suspected of alfa thalassemia carriage, then confirmed with mutation analysis with exclusion of iron deficiency anemia ve beta thalassemia (Normal ferritin level; HbA2<%3.5) at Adnan Menderes University Pediatric Hematology Department between January 1st 2010 and June 30th 2015 enrolled in the study. The mutations in alfa globin gene have been detected using ViennaLab α-globin StripAssay with reverse hybridization principle. The mutations which can not be detected with StripAssay, a mutation screening for alfa 1 and alfa 2 genes in DNA sequence analysis has been performed in 50 patients at Antalya Genetics Laboratory. Mindray BC-6800 has been used for CBC and Aqilent 110 has been used for hemoglobin electrophoresis with HPLC method. RESULTS We have detected 12 different genotypes and 11 different mutations in 52 alfa thalassemia patients (31 boys, 21 girls; median age 7.62±5.01). The most frequent 4 geontypes and 4 allells are α3,7/αα (40.4%), -α3,7/-α3,7(13.5%), --20,5/αα (11,5%), --MED/αα (9.6%) and -α3,7(33.65%), --20,5 (7.68%), --MED(4.8%), α2PolyA-1 (3.84%) respectively. Forty five of the mutations (%86.54) were deletional whereas, 7 of them were non-deletional. 33 of deletional mutations were single-gene deletions, and 11 of them were double-gene deletions. There was no statistical significant difference between single and double gene deletion groups in haemoglobin, red cells and RDW levels whereas a statistically significant difference has been detected in MCV (66.78±7.38 vs 60.69±3.1 fl), MCH (21.40±2.51 vs 19,30±1.11 pg) ve HbA2 (%2.52±0.34 vs %2.16±0.39) levels (p <0,001, <0,001, =0,006, respectively). Anemia 48,08%, microcytosis 92.31%, hypochromia 100%, red blood cell elevation 96.15%, RDW elevation 90.38% was detected proportionally in our patients. In 21 patients with the most frequent -α3,7/αα genotype, anemia 38.1%, microcytosis 85.71%, hypochromia 100%, red blood cell elevation 95.24% and RDW elevation 85.71% was detected respectively. HBA1:c328 del C heterozygotic mutation has been detected for the first time in our country. HBA2:c.93_95+2 del GAGGT mutation has been detected for the first time and can not be found in database around the world. CONCLUSION Acknowledgement of the type and the widespread of the mutations in alfa thalassemia patients in Aydin and peripherals will be of great value in prenatal diagnostic and consultancy care and also will be a valuable contribution in Turkey's alfa thalassemia mutation map. MCV, MCH and HbA2 levels can be useful in diferentiation of single and double gene deletions. RDW is not an appropriate tool in differential diagnosis of iron deficiency. Key words: Alfa thalassemia, mutations, hemoglobinapathy, anemia, children