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The aim of this study was to determine a possible association of IVS3 poly A and IVS10 CA microsatellites with CF in case–control Tunisian groups and to compare the results with the findings in Italian population. Both microsatellites were analyzed by capillary electrophoresis in 70 normal subjects and 60 Tunisian CF patients. The statistical distribution of IVS3 poly A and IVS10 CA polymorphism shows a significant difference between CF patients and controls group. 12 different alleles were found for IVS3 poly A which only five were identified in CF patients. IVS3 poly (A)19 was the most prevalent allele in CF patients with 75%. Nevertheless, IVS3 poly (A)18 was more common in normal individuals (27.14%). Seven different alleles were found for IVS10 CA. The IVS10 (CA)16 was the most prevalent allele both in normal individuals and CF patients with 30.71 and 52.5% frequencies respectively. Concerning the association of these two markers with F508del mutation, we noted that IVS3 poly (A)19 is the most common in our CF patients but IVS3 poly (A)18 is specific to the CF Italian patients. Furthermore, IVS10 (CA)16 and IVS10 (CA)19 are the most dominant (29.16%) in our samples and IVS10 (CA)23 is specific to the CF Italian subjects (94.4%). Our study allowed us to identify the haplotype distribution of both markers IVS3 poly A and IVS10 CA in CF and control subjects. The results obtained show a strong association between the most frequent F508del mutation and IVS3 poly (A)19, IVS10 (CA)16 and IVS10 (CA)19. [ABSTRACT FROM AUTHOR]

Beta-thalassemia is the most frequent hereditary blood disorder in Tunisia because of its geographic localization and history. This pathology is characterized by a complex multisystem process with genetic and biochemical interactions. The aim of this work was to establish phenotype/genotype association through studying the distribution and the relationship between β-thalassemia and α-thalassemia mutations and three polymorphic markers: the C → T polymorphism at −158 of the Gγ gene, the RFLP haplotype and the repeated sequence (AT)T in the β globin silencer, in two groups of β-thalassemia major and β-thalassemia intermedia (TI) patients. Statistical analysis has shown that moderate expression seen in TI patients was significantly associated to β −87 (C → G), −30 (T → A) and IVSI-6 (T → C) mutations, haplotypes VIII, IX and Nb and to XmnI polymorphism. The regression analysis of combined genotypes (mutation/ XmnI/RFLP haplotype) revealed that they contribute to justify 17.1 % of clinical expression diversity ( p < 0.05). Among the studied genotypes the XmnI polymorphism seems to be the most determinant modulating factor, followed by the β-thalassemia mutation and RFLP haplotype. Our findings highlight the heterogeneity of molecular background of β-thalassemia that would be responsible of clinical variability. [ABSTRACT FROM AUTHOR]

Unlike the other haemoglobinopathies, few researches have been published concerning α-thalassaemia in Tunisia. The aim of the present work is to acquire further data concerning α-thalassaemia prevalence and molecular defects spectrum in Tunisia, by collecting and studying several kinds of samples carrying α-thalassaemia. The first survey conducted on 529 cord blood samples using cellulose acetate electrophoresis, have displayed the prevalence of 7.38% Hb Bart's carriers at birth. Molecular analyses were conducted by PCR and DNA sequencing on 20 families' cases from the above survey carrying the Hb Bart's at birth and on 10 Hb H diseased patients. The results showed six α-globin gene molecular defects and were responsible for α-thalassaemia: -α3.7, --MedI, αTSaudi, αcd23GAG→Stop2, Hb Greone Hart: α119CCT→TCT1 corresponding to 11 genotypes out of which two are responsible for Hb H disease (--Med/-α3.7) and (αTSaudiα/αTSaudiα) and a newly described polymorphism: α+6C→G. The geographical repartition of α-thal carriers showed that the -α3.7 deletion is distributed all over the country, respectively the αHphI and αTSaudi seem to be more frequent in the central region of the northeast region. The haematological and clinical data showed a moderate phenotype with a late age of diagnosis for Hb H disease. This work had permitted, in addition to an overview on α-thalassaemia in the country, the optimization of protocols for α-thalassaemia detection in our lab, allowing further investigations concerning phenotype-genotype correlation in sickle cell disease or β-thalassaemia. [ABSTRACT FROM AUTHOR]

Abnormalities of coagulation and fibrinolysis were studied in a group of 28 children and young adults with homozygous sickle cell disease (SCD), either in the steady state (n = 12) or during painful crisis (n = 16). Coagulation was explored by standard clotting tests and by measurement of prothrombin complex factors, factor VIII (VIII:C) and antithrombin III (ATIII), protein C (PC) and protein S (PS) activities, while fibrinolytic potential was evaluated using D-dimer, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) assays. In SCD patients, thrombin time (TT) was constantly shortened, both in the steady state (ratio to control 0.83 ± 0.08, p < 0.0001) and in crisis (0.76 ± 0.06, p < 0.0001). Mean levels of prothrombin complex were similar in asymptomatic patients to those in controls, but were significantly decreased during sickle cell crisis (p < 0.05 for factor V and p < 0.0001 for factors II,VII and X). Factor VIII:C was significantly increased, both in the steady state (207 ± 35%, p < 0.0001) and during crisis (208 ± 34 %, p < 0,0001). PS activity was reduced in the steady state (81 ± 12%, p < 0.01) and further diminished in crisis (68.5 ± 27.5%, p < 0.001), while D-dimers were significantly elevated during sickle cell crisis (1028 ± 675 ng/ml, p < 0.001). In all SCD patients, baseline levels of t-PA antigen were comparable to those in controls, whereas concentrations of PAI-1 antigen were significantly increased, either in the steady state (89.7 ± 26.3 ng/ml, p < 0.0001) or in crisis (75.0 ± 24.8 ng/ml, p < 0.0001). These results provide evidence for the presence of circulating activated clotting factors in SCD and for an imbalance of the profibrinolytic and antifibrinolytic systems most likely due to increased PAI-1 levels. [ABSTRACT FROM AUTHOR]