In patients with β-thalassemia iron overload that leads to damage to vital organs is observed. Glutathione S transferase (GST) enzymes have an antioxidant role in detoxification processes of toxic substances. This role is determined genetically. In this study, we correlated GSTT1 and GSTM1 genotypes with iron overload measured with direct and indirect non-invasive methods; in particular, we used serum ferritin and signal intensity of the magnetic resonance image (MRI) in 42 patients with β-thalassemia, which were regularly subjected to chelation and transfusion therapy. Multiplex polymerase chain reaction was used to determine the genotype. The loss of both alleles leads to a decreased value of liver and heart MRI-signal intensity with a consequent iron accumulation in these organs; the loss of only one allele doesn't lead to relevant overload. Serum ferritin doesn't appear to be correlated to iron overload instead.

Increased expression of fetal hemoglobin (HbF) may ameliorate the clinical course of hemoglobinopathies. Hydroxyurea (HU) is the only inducer approved for the treatment of these diseases able to stimulate HbF production but patients’ response is highly variable indicating the utility of the identification of pharmacogenomic biomarkers in order to predict pharmacological treatment efficacy. To date few studies to evaluate the role of genetic determinants in HU response have been conducted showing contradictory results. In this study we analyzed BCL11A, GATA-1, KLF-1 genes and γ-globin promoter in 60 alleles from 30 hemoglobinopathies patients under HU treatment to assess the role of these markers in HU response. We did not find any association between these genetic determinants and HU response. Before treatment started, the same patients were analyzed in vitro using liquid erythroid cultures in a test able to predict their response to HU. The results of our analysis confirm the absence of pharmacogenomic biomarker associated to HU response indicating that, the quantification of γ-globin mRNA fold increase remains the only method able to predict in vivo patients response to the drug.

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Background: Cystic Fibrosis (CF) is a genetic disease which is responsible for different systemic conditions. In particular, CF could be responsible for infertility, especially in the male partner due to congenital bilateral absence of vas deferens (CBAVD). Moreover, in Assisted Reproductive Techniques CF screening is performed in order to detect possible risks for the newborn. For this reason, CF testing is one of the main genetic screening performed in infertile couples. Methods: In this scenario, we present a prospective observational study in CF testing with Next Generation Sequencing (NGS) technique on 360 subjects referring to an In-Vitro Fertilization center. Results: 360 subjects were screened for CFTR. Of them, 19 subjects presented CF causing variants, 44 subjects presented CFTR-RD associated, 22 subjects had variants of uncertain significance and 19 subjects with no clinical consequences. Conclusion: Results clarify proportions of the main CF mutations. Actually, there are no more advanced techniques rather than Next Generation Sequencing (NGS) technique, although it is not yet widely used as a test for the identification of the CF carrier.

The hemoglobinopathies, as β-thalassemia (β-thal) and sickle cell disease, are the most common hereditary hemolytic anemias. The increase of fetal hemoglobin (Hb F) levels can ameliorate the symptoms of hemoglobinopathies. There are several transcription factors such as MYB and SOX-6, which are involved in the regulation of Hb F. There are not enough studies investigating the association between single nucleotide polymorphisms (SNPs) of the SOX-6 and MYB genes and the variation of Hb F levels in patients affected by sickle cell disease and β-thal. We therefore decided to analyze the role of four missense variants of MYB and SOX-6 genes in the regulation of Hb F levels. In order to do so, we examinated 30 Sicilian patients affected by sickle cell disease and β-thal, to understand if these variants could also have an influence in our populations. Comparing two groups of patients with low and high levels of Hb F, we found no significant differences in the genetic distribution and allelic frequency of MYB and SOX-6 gene polymorphisms. We also created and compared a 'high producer' and 'low producer' genotype with different genes achieving the same result of no significant difference. Our results may be due either to the fact that the association between these genes and the regulation of Hb F levels are influenced by environmental history and population genetics, or to the small number of samples being analyzed.