Evaluation of Beta Globin Gene Mutations in Beta Thalassemia Carrier Children in Aydın Province and its Environment

Abstract

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: The study population with a mean age 8.34±4.94 years consisted of 39 (60.0%) male, and 26 (40.0%) female patients. When full blood count parameters were analyzed, 87.7% of the patients had anemia, 100% microcytosis and high red cell distribution width (RDW), 49.2% hypochromia and 87.7% increased red blood cell (RBC) counts. 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 mutations were heterozygous IVS I-110 mutation in 44.11%, heterozygous IVS I-1 G>A mutation in 8.8%, heterozygous IVS I-6 T>C mutation in 7.5% and IVS II-745 mutation in 7.5% of the patients. 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. Most commonly IVS I-110 (44.11%), heterozygous IVS I-1 G>A (8.8%) heterozygous IVS I-6 T>C (7.5%) and IVS II-745 (7.5%) mutations were observed. In patients with IVS I-110 mutation, average values for Hb (10.55 gr/dL), MCV (58.44 fL), RDW (16.51%), RBC (5680x10⁹/L), HbA2 (4.77%), HbF (2.34%) were as indicated. Mutations detected in 12 patients with HbF level above 5% including: cases with IVS I-110 (n=5) mutations, heterozygous IVS I-6 T>C, Codon 39 C>T IVS I-116, c.25-26 del AA (plys9Valfs), c.27dupG (pSer10valfs*14), c316-373 (IVS II-478 C>A, and-87 C>T mutations. 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, and-87 C>T heterozygotes. There were four patients (6.1%) with a RDW index of >220. Two of these patients had c.27dupG (p.Ser10valfs*14) and others had heterozygous c316-373 (IVS II-478 C>A and-87 C>T mutations. Mutations detected in four patients with HbF levels in the range of 9.48-15.67 and the patients had heterozygous IVS I-116 T>G, IVS I-110 G>A, c.25-26 del AA (p.lys59valfs), and c27 dupG (pSer10 valfs*14) mutations, 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) 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 which suggests 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 of ≥13 and RDW index of ≥220, HbA2 <3.5 and studying the mutation analysis of these patients will contribute significantly to the literature.