Contribution to the description of the beta-thalassemia spectrum in Tunisia and the origin of mutation diversity

We determined the spectrum of beta-thalassemia (thal) mutations in 118 affected unrelated patients with different forms of beta-thal. Using a combination of reverse dot-blot analysis, denaturing gradient gel electrophoresis (DGGE), polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) and direct nucleotide sequencing, we identified the largest spectrum of beta-thal mutations so far reported in Tunisia, and to the best of our knowledge, within the Mediterranean Basin. A total of 18 distinct alleles were detected at different frequencies, with two alleles [codon 39 (C-->T) and IVS-I-110 (G-->A)] predominating all others. Seven other alleles [frameshift at codon (FSC) 6 (-A), FSC 8 (-AA), codon 30 (G-->C), IVS-I-1 (G-->A), IVS-I-2 (T-->G), IVS-I-6 (T-->C), FSC 44 (-C)] were rare, and nine alleles [-29 (A-->G), IVS-I-2 (T-->C), IVS-I-5 (G-->C), IVS-I-5 (G-->T), IVS-I-116 (T-->G), codon 37 (G-->A), IVS-II-1 (G-->A), IVS-II-745 (G-->C) and IVS-II-849 (A-->C)], albeit described elsewhere, are reported here in Tunisia for the first time. The codon 39 and IVS-I-110 mutations were the two predominant alleles occurring at frequencies of 43.8% and 10.8%, respectively. They are presumably the earliest mutations introduced into this country. The codon 39 allele could have been introduced in Tunisia during the Roman occupation. Similarly, the IVS-I-110 mutation might have been introduced by the Turkish and Phoenician influence. Both gene flow and private mutations may account for the diversity of alleles observed in Tunisia. These data provide the background for implementing prevention programs based on genetic counseling and prenatal diagnosis.     

Effectiveness,safety and drug survival of tumor necrosis factor-α inhibitors in the treatment of spondyloarthritis: A real-life study in Tunisia

Aim of the work

The aim of the present study was to evaluate effectiveness of anti-tumor necrosis factor-α (anti-TNFα) in the treatment of spondyloarthritis (SpA) and to assess their safety and drug survival.

Hb Moscva [β24(B6)Gly→Asp (GGT>GAT), HBB: c.74G>A]: An Unstable Hemoglobin Newly Detected as a De Novo Mutation in a Mauritanian Patient

Unstable hemoglobins (Hbs) are a group of Hb disorders that could be the origin of chronic hemolytic anemia. Most of these disorders are caused by point mutations taking place in the globin genes and affecting the stability of the Hb molecule. They are inherited as autosomal dominant diseases and described worldwide. Herein we report a new observation of an unstable variant in the Mauritanian population. The patient was a young girl of Mauritanian origin. She presented with chronic hemolytic anemia with an unknown etiology after being referred to several medical centers. Laboratory investigations based on routine analyses, capillary electrophoresis (CE), cation exchange high performance liquid chromatography (HPLC) and DNA sequencing revealed an abnormal unstable Hb known as Hb Moscva [β24(B6)Gly→Asp (GGT>GAT), HBB: c.74G>A] that occurred as a de novo mutation newly detected in an African girl of Mauritanian origin.     

Expression of epidermal growth factor receptor (EGFR) in colorectal cancer: An immunohistochemical study

Background and study aim

The epidermal growth factor receptor (EGFR) plays an important role in tumourigenesis and tumour progression of colorectal cancer (CRC) and leads to the activation of intracellular signaling pathways. The use of anti-EGFR-targeted therapy has increased for patients with metastatic CRC. Today, the clinical utility of immunohistochemistry has remained somewhat inconclusive. It is based on EGFR screening methods using paraffin-embedded tumour specimen to select patients eligible for treatment. There is still lack of agreement on reproducible scoring criteria for EGFR immunohistochemistry has in various clinical trials.

Total absence of ST-segment resolution after failed thrombolysis is correlated with unfavorable short- and long-term outcomes despite successful rescue angioplasty

Introduction

ST-segment resolution (STR) is a well-established and simple tool for assessing the efficacy of reperfusion therapy in myocardial infarction. An incomplete (<50%) STR is a recognized marker of failed thrombolysis and a suitable recruitment criterion for rescue angioplasty.

Objective

We sought to determine the predictive value of the total absence of STR after thrombolysis in rescue angioplasty (percutaneous coronary intervention [PCI]).

Methods

Eighty-one consecutive patients who underwent a rescue angioplasty for failed thrombolysis in our institution from 2001 to 2007 were included. Two groups of patients were defined according to their STR extent, 90 minutes after lysis: partial resolution group 1 (10%-50% STR) vs absence of resolution group 2 (<10% STR) and compared in terms of in-hospital and long-term outcomes.

Results

Patients of group 2 were more likely to experience hemodynamic deterioration (50% vs 24%; odds ratio [OR] = 3.17; P = .017), to have a Thrombolysis in Myocardial Infarction 0 flow on the culprit artery (62.3% vs 42%; OR = 2.24; P = .045), to have a multivessel disease (66.7% vs 40%; OR = 3; P = .018), and to die during index hospitalization (26.7% vs 6%; OR = 5.69; P = .013) despite statistically similar rates of PCI failure in both groups (10% vs 7%; P = .402) and similar post-PCI STR (72% ± 18.25% vs 75% ± 11.62%; P = .36). In multivariate analysis, total absence of STR proved to be an independent predictor of in-hospital mortality (HR = 7.02; P = .032; 95% confidence interval, 1.18-41.58). Long-term major adverse cardiac events occurred more frequently in group 2 (log rank, P = .004) and were (on the Cox regression model) independently predicted by total absence of STR (HR = 6.21; P = .023; 95% confidence interval, 1.28-29.1).

Conclusions

The STR assessment before rescue PCI proved to be a good and simple means to predict the short- and long-term prognosis in these patients.     

The role of rs1984112_G at CD36 gene in increasing reticulocyte level among sickle cell disease patients

Aims and background: Mediators of adhesion become a potential new target for pharmacological therapy to struggle the complications of sickle cell disease (SCD). Several mechanisms for increased adherence have been postulated and the well-studied are CD36 and VLA4 which encoded by ITGA4. Herein, we sought to determine whether one polymorphism of CD36 namely: rs1984112 and three exons of ITGA4 (4, 5, and 6) are implicated in hemolytic status and clinical events among SCD Tunisian patients.

Material and methods: This study enrolled 99 unrelated Tunisian subjects (63SS and 36Sβ). All SCD patients are children (less than 16 years old). The rs1984112 and the ITGA4’s exons 4, 5, and 6 were analyzed for all subjects by PCR/sequencing. The association of each genotype found with both clinical complications and hemolytic status was performed using t-test. Clinical events studied included vaso-occlusive crisis (VOC), osteonecrosis, stroke, frequent infection, priapism, and acute syndrome.

Results: The results show that rs1984112_G allele at CD36 gene revealed to be associated with higher levels of reticulocyte count (p?p?=?0.051). No association between rs1984112_G allele and the clinical severity of SCD were found. Mutational screening of exon 4, 5, and 6 of ITGA4 gene revealed absence of mutated variant.

Conclusion: Our results are similar to those found in Portuguese population which reported the role of rs1984112_G in increasing reticulocyte level among SCD patients. Consequently, the rs1984112_G of CD36 could be considered as a reliable biomarker for predicting patients at high risk for vascular occlusions and thus, allows earlier and more effective therapeutic management.     

Natural evolution of hepatitis C virus infection in hemodialysis Tunisian patients and CTLA-4 SNP's

AIM: To analyze the polymorphisms of CTLA-4 gene involved in the response against hepatitis C virus(HCV) infection.METHODS: We recruited 500 hemodialysed patients from several hemodialysis centers, all HCV-antibody positive, spread over different regions of Tunisia, as part of a national survey in 2008 conducted in the laboratory of immunology at the Charles Nicolle hospital Tunisia, classified into two groups G1(PCR+) and G2(PCR-) according to the presence or absence of viral RNA. Of these patients, 307 were followed prospectively on a viral molecular level over a period from 2002 to 2008, divided into two groups based on the persistence and viral clearance. PCR-RFLP was performed for the analysis of SNPs(+49) A/G and(+6230) G/A CTLA-4 for these 500 patients and 358 healthy controls.RESULTS: Analysis of clinical and virological charac-teristics of our cohort suggests a nosocomial infection in our hemodialysed patients with transfusion history as a primary risk factor and a predominance of genotype 1b. The haplotype analysis revealed an increase of frequencies of GG(+49)/(CT60) CTLA-4 in the entire patients group compared to controls(P = 0.0036 and OR = 1.42; 95%CI: 1.12-1.79, respectively). This haplotype is therefore associated with susceptibility to HCV infection. CONCLUSION: Our study suggests a possible role of CTLA-4 polymorphisms in the outcome of HCV infection in the Tunisian hemodialysed population.     

Multiple endocrine neoplasia type 1 revealed by a hip pathologic fracture

Clinical Rheumatology - Multiple endocrine neoplasia type 1 is a rare autosomal inherited syndrome that affects a variety of endocrine tissues such as the parathyroid, endocrine pancreas, and...