Contributions
Abstract: PB2500
Type: Publication Only
Background
Azerbaijan is one of the countries with the highest prevalence of thalassemias. β-Thalassemia is known for its extremely diverse clinical manifestations. Therefore, determination of factors causing such a diverse clinical presentation has clinical significance, and the major reason for such diversity is the variety of mutations. A number of studies revealed genotype-to-phenotype correlations of β-thalassemia mutations in various populations, and we hereby report the first one conducted in an Azerbaijani population.
Aims
The aim of our study was to reveal genotype-to-phenotype correlations of the most common β-thalassemia mutations in an Azerbaijani population.
Methods
48 patients (23 heterozygous, 23 homozygous, 2 compound heterozygous β-thalassemia) with known genotypes were included in the study. Evaluations of RBC count, hemoglobin concentration, hematocrit, MCV, MCH, and MCHC were performed with a Sysmex XT2000i hematology analyzer. All samples were tested for hemoglobin fractions by high-performance liquid chromatography via the VARIANT II Hemoglobin Testing System (Bio-Rad). DNA amplification was performed on a C-1000 thermocycler (Bio-Rad). Detection of mutations by reverse dot-blot hybridization was performed with commercial test kits (β-Globin StripAssay Kit, ViennaLab) according to the manufacturer’s instructions. One-way ANOVA followed by Tukey’s honestly significant difference test was used to analyze between-group differences.
Results
The classical β-thalassemia carrier pattern of increased RBC count and low hemoglobin and erythrocyte indices (MCV, MCH, and MCHC) was observed in almost all patients. Increased HbA2 concentrations and fetal hemoglobin within the normal range (<2%) were observed in most cases. There was a statistically significant difference (p<0.05) in RBC, MCV, and MCH parameters of IVS-I-6 patients compared to the groups with codon 8 and IVS-II-1. The former was associated with comparably lower RBC and higher MCV and MCH mean values. Based on this pattern of hematologic data, it can be concluded that IVS-I-6 presents a milder phenotype compared to codon 8 and IVS-II-1 mutations. No statistically significant difference was obtained between codon 8 and IVS-II-1 mutations (p>0.05). The data of homozygous individuals were also observed to correlate with the type of the mutation. Statistically significant between-group differences (p<0.05) were observed for MCV, MCH, and MCHC. Contrary to the heterozygous individuals, lower mean values of these parameters were observed in the group of homozygous IVS-I-6 patients, possibly due to their less frequent transfusions, compared to codon 8 and IVS-II-1 patients. The results obtained indicate that clinical presentation varies between different β-globin gene mutations: individuals with IVS-I-6 (T>C) mutations showed milder presentation than those with codon 8 (-AA) and IVS-II-1 (G>A), which is associated with the molecular basis of the mutations.
Conclusion
Our study revealed genotype-to-phenotype correlations of the most prevalent β-thalassemia mutations of the Azerbaijani population. According to our data, hematologic parameters and consequently the clinical presentation are closely related to the type of the mutation, especially in homozygous patients. Our findings can provide a better prediction of clinical manifestation by early identification of the type of the β-thalassemia mutations.
Session topic: 28. Thalassemias
Keyword(s): Thalassemia
Abstract: PB2500
Type: Publication Only
Background
Azerbaijan is one of the countries with the highest prevalence of thalassemias. β-Thalassemia is known for its extremely diverse clinical manifestations. Therefore, determination of factors causing such a diverse clinical presentation has clinical significance, and the major reason for such diversity is the variety of mutations. A number of studies revealed genotype-to-phenotype correlations of β-thalassemia mutations in various populations, and we hereby report the first one conducted in an Azerbaijani population.
Aims
The aim of our study was to reveal genotype-to-phenotype correlations of the most common β-thalassemia mutations in an Azerbaijani population.
Methods
48 patients (23 heterozygous, 23 homozygous, 2 compound heterozygous β-thalassemia) with known genotypes were included in the study. Evaluations of RBC count, hemoglobin concentration, hematocrit, MCV, MCH, and MCHC were performed with a Sysmex XT2000i hematology analyzer. All samples were tested for hemoglobin fractions by high-performance liquid chromatography via the VARIANT II Hemoglobin Testing System (Bio-Rad). DNA amplification was performed on a C-1000 thermocycler (Bio-Rad). Detection of mutations by reverse dot-blot hybridization was performed with commercial test kits (β-Globin StripAssay Kit, ViennaLab) according to the manufacturer’s instructions. One-way ANOVA followed by Tukey’s honestly significant difference test was used to analyze between-group differences.
Results
The classical β-thalassemia carrier pattern of increased RBC count and low hemoglobin and erythrocyte indices (MCV, MCH, and MCHC) was observed in almost all patients. Increased HbA2 concentrations and fetal hemoglobin within the normal range (<2%) were observed in most cases. There was a statistically significant difference (p<0.05) in RBC, MCV, and MCH parameters of IVS-I-6 patients compared to the groups with codon 8 and IVS-II-1. The former was associated with comparably lower RBC and higher MCV and MCH mean values. Based on this pattern of hematologic data, it can be concluded that IVS-I-6 presents a milder phenotype compared to codon 8 and IVS-II-1 mutations. No statistically significant difference was obtained between codon 8 and IVS-II-1 mutations (p>0.05). The data of homozygous individuals were also observed to correlate with the type of the mutation. Statistically significant between-group differences (p<0.05) were observed for MCV, MCH, and MCHC. Contrary to the heterozygous individuals, lower mean values of these parameters were observed in the group of homozygous IVS-I-6 patients, possibly due to their less frequent transfusions, compared to codon 8 and IVS-II-1 patients. The results obtained indicate that clinical presentation varies between different β-globin gene mutations: individuals with IVS-I-6 (T>C) mutations showed milder presentation than those with codon 8 (-AA) and IVS-II-1 (G>A), which is associated with the molecular basis of the mutations.
Conclusion
Our study revealed genotype-to-phenotype correlations of the most prevalent β-thalassemia mutations of the Azerbaijani population. According to our data, hematologic parameters and consequently the clinical presentation are closely related to the type of the mutation, especially in homozygous patients. Our findings can provide a better prediction of clinical manifestation by early identification of the type of the β-thalassemia mutations.
Session topic: 28. Thalassemias
Keyword(s): Thalassemia