Search

Background: Deletions in the β-globin cluster are uncommon and cause thalassemia (thal) with hereditary persistence of fetal hemoglobin. They constitute a heterogenous group of disorders characterized by absent or reduced synthesis of adult hemoglobin (Hb A) and increased synthesis of fetal hemoglobin (Hb F). Although the clinical severity of these disorders are asymptomatic owing to the increased Hb F levels, the molecular basis is very heterogenous due to the large deletions in the β-globin cluster spanning both HBD and HBB genes. Here, we describe a Tunisian family carrying a novel deletion mutation causing (δβ)°-thalassemia. Methods: The amounts of hemoglobin fractions were measured by capillary electrophoresis of hemoglobin. Amplification and sequencing of different regions on the β-gene cluster were performed by Sanger method. Results: Family study and genetic analysis revealed a large deletion mutation in the β-globin cluster of 14.5 kb (NG_000,007.3:g. 58,253 to g.72837del14584) at the homozygous state in the patient and at heterozygous state at the other members of the family. This deletion removes the HBD and HBB genes. Conclusions: In our knowledge, this new large deletion is described for the first time in the Tunisian population and in the world, designed Tunisian(δβ)0 in Ithanet database (IthaID: 3971). Therefore, it is important to identify the deletion leading to δβ-thalassemia carriers at the molecular level, to highlight the importance of recognizing the clinical features and implementing appropriate testing to clarify the diagnosis and manage the condition. [ABSTRACT FROM AUTHOR]

Objectives Different thalassemia mutations have been reported in various ethnic groups and geographical regions in Tunisia. In the present study, we have investigated two rare β+-thalassemia mutations, that have not previously been reported in the Tunisian population [ β −56 (G > C); HBBc. −106 G > C] and [ β −83 (G > A); HBBc. −133 G > A]. Methods The whole β-globin gene was directly sequenced, and haplotype analysis was conducted through a PCR/RFLP method. Results: Two new mutations were identified for the first time in Tunisia. They are located within the promoter region of β-globin gene at position −56 (G > C) and −83 (G > A). Linkage analysis using β-globin gene cluster haplotypes showed that these two mutations were associated with Mediterranean β-haplotype IX [− + − + + + +] and framework 2 (FW2) [ CCTCT]. Conclusions The two newly described mutations lead to the β+-thalassemia among Tunisian patients. The haplotype analysis and framework assignment have helped to identify the chromosomal background associated with these mutations, and determine their origin and spread. Am. J. Hum. Biol. 27:716-719, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

We investigated the association of the lymphotoxin ( LT)-α gene polymorphism +249A/G with type 1 diabetes. The distribution of genotypes of the LT- α +249A/G single nucleotide polymorphism (SNP) was assessed in 115 diabetic patients and 123 normoglycemic control subjects, using PCR-restriction fragment length polymorphism analysis. Among unselected patients, the SNP was significantly associated with increased risk of diabetes (χ = 8.44, p = 0.014) and was found to be more pronounced among female (χ = 8.37, p = 0.02) than male (χ = 6.11, p = 0.047) patients. A significant association was detected between LT- α +249A/G and increased risk of diabetes, in particular for young-onset patients (χ = 6.92, p = 0.031). Moreover, we reported significant differences in levels of HbA1c, triglycerides, alanine transaminase, and anti-glutamic acid decarboxylase-65 among alleles. Additional studies with extended patient age groups and different ethnicities are needed to confirm our findings. [ABSTRACT FROM AUTHOR]