Objective: Beta thalassemia carriers (BTC) in Turkey is observed with a frequency of 2.1%, and it is the most common cause of anemia after iron deficiency. There are few studies showing the effect of genotype on phenotype in beta thalassemia carrying children. The aim of this study is to determine the mutation diversity of these children in and around Aydın and evaluate the effects of these mutations on complete blood count parameters and hemoglobin electrophoresis.

Methods: This study included mutation analysis of 65 patients who were diagnosed as BTC in Adnan Menderes University, Faculty of Medicine, Department of Child Health and Diseases, Pediatric Hematology Outpatient Clinic between 01.01.2014 and 01.08.2019. Complete blood count, hemoglobin electrophoresis and mutation analysis results were obtained from the computer data system and patient files. Research data were evaluated by using SPSS 21.0 statistics program.

Results: 39 (60.0%) of the sixty-five patients were male, 26 (40.0%) were female, and the mean age was 8.34±4.94 years. When full blood count parameters were analyzed, 87.7% had anemia, 100% microcytosis and high red cell distribution width (RDW) level, 49.2% hypochromia and 87.7% high red blood cell (RBC) count. RDW level was ≥16 in 66.2% of the cases. Seventeen different mutations were detected. The mutations most frequently occurred in “intron 1” gene region (66.1%). The most common ones were IVS I-110 (44.11%), IVS I-1 G>A Heterozygotes (8.8%,) IVS I-6 T>C Heterozygotes (7.5%) and IVS II-745 (7.5%). RDW level was ≥16 in 66.2% of the cases. Seventeen different mutations were detected. The mutations most frequently occurred in “intron 1” (66.1%) gene region. IVS I-110 (44.11%), IVS I-1 G>A Heterozygotes (8.8%,) IVS I-6 T>C Heterozygotes (7.5%) and IVS II-745 (7.5%) were observed most commonly. In patients with IVS I-110 mutation, mean Hb level was 10.55 gr/dL, MCV level was 58.44 fL, RDW level was 16.51, RBC level was 5680x10⁹/L, HbA2 level was 4.77%, HbF level was 2.34%. Mutations detected in 12 patients with HbF level above 5% were as IVS I-110 (5 people), IVS I-6 T>C Heterozygotes, Codon 39 C>T Heterozygotes, IVS I-116, c.25-26 del AA (plys9Valfs) Heterozygotes, c.27dupG (pSer10valfs*14), c316-373 (IVSII-478 C>A Heterozygotes), -87 C>T Heterozygotes. Mentzer index was calculated as >13 in six patients (9.2%). The mutations seen in these patients were IVS-I 110, c.27dupG (p.Ser10valfs*14), c316-373 (IVS II-478 C>A Heterozygotes), -87 C>T Heterozygotes. There were four patients (6.1%) with a RDW index >220. Two of these patients had c.27dupG (p.Ser10valfs*14) and others had c316-373 (IVS II-478 C>A Heterozygotes) and -87 C>T Heterozygotes mutations. Mutations detected in four patients with HbF levels in the range of 9.48-15.67 were IVS I-116 T>G Heterozygotes, IVS I-110 G>A Heterozygotes, c.25-26 del AA (p.lys59valfs) Heterozygotes, c27 dupG (pSer10 valfs*14) and three of these mutations carrying β° mutation type were located in exon 1 and one of them carrying β⁺ mutation type (IVS I-110) was in intron 1.

Conclusion: The same mutations detected in patients with beta thalassemia carriers have different effects on complete blood count parameters. HbA2 and HbF levels suggest that these mutations are not effective on the phenotype alone and there may be additional factors which should be clarified. We think that there may be BTC in cases with low RBC, Mentzer index ≥13 and RDW index ≥220, HbA2 <3.5 and studying the mutation analysis of these patients will contribute significantly to the literature.

Keywords: Beta thalassemia carriers, complete blood count parameters, beta globin gene mutations, hemoglobin electrophoresis