First Report of ß-Thalassemia Intermedia in a Patient Compound Heterozygous for -92 (C>T) and Codons 36/37 (-T) Mutations.

The -92 (C>T) (HBB: c.-142C>T) is a silent ß-thalassemia (ß-thal) mutation previously described in combination with several ß0 mutations and expressed as ß-thal intermedia (ß-TI). Heterozygous individuals are known to be completely asymptomatic showing borderline hemoglobin (Hb), mean corpuscular volume (MCV) and Hb A2 levels. Here, we report the first incidence of -92 in Eastern Europe and in Azerbaijan, and the first case in combination with codons 36/37 (-T) (HBB: c.112delT) mutation.

Molecular and geographical heterogeneity of hemoglobinopathy mutations in Azerbaijanian populations.

With the carrier rate of 4%-8.6%, ß-thalassemia is one of the most prevalent hereditary disorders in Azerbaijan. Taking into consideration the high frequency of ß-thalassemia as well as the occurrences of several other hemoglobinopathies, we conducted a large genotyping study to investigate the mutational background of common hemoglobinopathies in the country. Α- and ß-globin genes were evaluated in the carriers of mutations identified via hematological indices and hemoglobin fractions (n = 1,757). Genotyping of ß-thalassemia carriers identified through population screening revealed 32 mutations, with codon 8 [-AA]-34.96%, IVS-II-1 [G > A]-16.35%, and IVS-I-110 [G > A]-10.12% leading the spectrum. Analysis of associations of ß-thalassemia mutations with geographical regions of the country identified the strongest association between codon 8 [-AA] and Shaki-Zaqatala, and codon 5 [-CT] in Mountainous Shirvan regions (ri > 6.00; p < 0.05). HbS, HbD-Punjab, and HbE were the most prevalent among our variant hemoglobin cohort, commonly inherited in compounds with ß-thalassemia than in the homozygous state. We identified nine α-thalassemia mutations, 20.5 kb and 3.7 kb deletions together accounting for 74% of the spectrum. Point mutations of α-thalassemia were less common among our observations and were mainly inherited in compounds with deletions. Our results allow a better understanding of the wide spectrum of mutations in Azerbaijan and highlights the high heterogeneity of hemoglobinopathies in the local population.

A Novel Frameshift Mutation at Codon 2 (-T) (HBB: c.9delT) and First Report of Three New ß-Globin Mutations From Azerbaijan.

We identified a novel mutation of ß-thalassemia (ß-thal) in a heterozygous carrier from Azerbaijan. Phenotypical data and molecular mechanisms of codon 2 (-T) (HBB: c.9delT) was relevant to ß0-thal. Additionally, we here report two new mutations on the HBB gene, not observed previously, in the local population as well as a non causative promoter mutation -198 (A>G) (HBB: c.-248A>G).

Codon 14 (+T) (HBB: c.44_45insT): a Rare ß-Thalassemia Mutation Reported Only in Azerbaijan.

Codon 14 (+T) (HBB: c.44_45insT) is a very rare ß-thalassemia (ß-thal) mutation previously reported in three ß-thal major (ß-TM) patients of Azerbaijani origin. None of the previous reports described the genotype-phenotype correlation of the mutation. We here report the first case of homozygous codon 14 together with data of the heterozygous parents.

Thalassemia in the laboratory: pearls, pitfalls, and promises.

Thalassemia is one of the most common hereditary disorders of the developing world, and it is associated with severe anemia and transfusion dependence. The global health burden of thalassemia has increased as a result of human mobility and migration in recent years. Depending on inherited mutations, thalassemia patients exhibit distorted hemoglobin (Hb) patterns and deviated red cell indices, both of which can be used to support identification by diagnostic tools. Diagnostic approaches vary depending on the target population and the aim of the testing. Current methods, which are based on Hb patterns, are used for first-line screening, whereas molecular testing is needed for conformation of the results and for prenatal and preimplantation genetic diagnosis. In the present paper, we review the diagnostic parameters, pitfalls, interfering factors, and methods; currently available best-practice guidelines; quality assurance and standardization of the procedures; and promising laboratory technologies for the future of thalassemia diagnosis.

Genotype-Phenotype Correlations of ß-Thalassemia Mutations in an Azerbaijani Population.

ß-Thalassemia is the most common inherited disorder in Azerbaijan. The aim of our study was to reveal genotype-to-phenotype correlations of the most common ß-thalassemia mutations in an Azerbaijani population. Patients with codon 8 (-AA), IVS-I-6 (T>C), and IVS-II-1 (G>A) mutations, which are reportedly the most common ß-globin gene mutations among the local population, were tested for hematologic parameters. Fifty-five previously tested patients with known genotypes were included in the study. Hematologic indices and hemoglobin fractions were tested in order to reveal the phenotypic manifestation of the mutations. The results obtained indicate that clinical presentation varies between different ß-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. These data can be of assistance to predict clinical presentation and select the best possible therapeutic approach via early genotype identification.