Severe phenotypes in two Tunisian families with novel XPA mutations: evidence for a correlation between mutation location and disease severity

Xeroderma pigmentosum (XP) is a rare disorder characterized by a high skin sun-sensitivity predisposing to skin cancers at an early age. Among Tunisian XP patients with an intermediate skin phenotype, 92% presented neurological abnormalities related to XPA gene deficiency. Clinical variability of the XP-A phenotype is associated with a mutational heterogeneity. In the present study, two Tunisian families with severe dermatological and neurological XP phenotypes were investigated in order to determine clinical characteristics and genetic basis. Two Tunisian families with four XP affected children were examined in the Dermatology Department. Clinical features showed severe presentation of the disease. Coding regions of the XPA gene were analysed by direct sequencing. Results showed the presence of a novel mutation, p.E111X, in three patients belonging to the same family and presenting a very severe phenotype i.e. development of skin lesions and neurological signs before 1 year age. For the other patient, we identified a nonsense mutation, p.R207X, already identified in a Palestinian XP-A patient. Identification of novel causing mutations in Tunisian XP-A patients shows the genetic and mutational heterogeneity of the disease in Tunisia. Despite a relatively homogenous mutational spectrum, mutational heterogeneity for rare cases is observed because of the high rate of consanguinity.     

Maternal benefit of postpartum corticosteroid therapy in patients with HELLP (hemolysis elevated liver enzymes low platelets count) syndrome

Our purpose was to assess the effects of corticotherapy prescribed after delivery on the kinetic of biological parameters of HELLP syndrome (hemolysis elevated liver enzymes low platelets count). Twenty patients in whom pregnancy was complicated by antepartum or postpartum Hellp Syndrome, were randomised to receive, after delivery, either 12 mg of Dexamethasone every 12 hours for two doses (Group C, n=10), or a placebo (Group T, n=10). Biological parameters of the Hellp syndrome were analysed just before the first bolus of either treatment (H0), then after 24, 36, 48 and 72 hours. The corticotherapy was more efficient than placebo, in the correction of the biological parameters of the hellp syndrome. It permitted a rapid correction of the thrombopenia (from the 24th hour) but its effect on hemolysis marker was later (from the 36th hour). The kinetic of the hepatic cytolysis marker was not modified by corticotherapy. Finally, the administration of corticosteroids does not reduce maternal morbidity related to HELLP Syndrome.     

Colorectal Cancer Incidence Trend and Projections in Tunisia (1994 - 2024)

Objectives: The aim of this study was to describe trends of colorectal cancer incidence during the period 1994-2009 and to generate projections until 2024. Methods: The North-Tunisia Cancer Registry (NTCR) was the source of data for patients with CRC. This registry lists, since 1994, cases of malignant tumors in people living in North Tunisia, including the District of Tunis, the north east and the north west. Cases were classified using the International Classification of Diseases for Oncology. Data were analyzed using R software and Joinpoint one was employed to analyse trends. Projections were performed using the Age Period Cohort based on poisson regression. Results: During the period 1994 to 2009, 6,909 new cases of CRC were registered in Northern Tunisia. The age standardized incidence rate (ASR) increased significantly from 6.4/100,000 in 1994 to 12.4/100,000 in 2009. Trends in CRC incidence was significantly rising with an annual percentage change (APC) of + 3,9% [2.8% -5.1%]. Without effective interventions, the predicted CRC ASR would be 39.3/100,000 [CI 95%: 32,9/100,000 - 48,8/100,000] in 2024. Conclusion: The incidence of colorectal cancer is clearly increasing in Tunisia. Strengthening of screening and primary prevention measures is to be recommended.     

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.     

Haplotypic classification of dystrophic epidermolysis bullosa in Tunisian consanguineous families: implication for diagnosis

Dystrophic epidermolysis bullosa (DEB) is a rare genodermatosis caused by mutations in the type VII collagen gene COL7A1. Clinical diagnosis of DEB should be confirmed by histopathological and electron microscopy analysis, which is not always accessible. We report here a genetic investigation of DEB consanguineous families in Tunisia. A total of 23 EB families were genotyped with 5 microsatellite markers overlapping the COL7A1 gene. Among these families, 19 presented with the dystrophic form of EB, 9 were diagnosed by histopathological examination, 2 had the simplex form, 1 had a junctional EB, and 1 was affected by an unclassified form of EB. The informativeness of the markers was studied and allowed us to select three markers for genetic testing of DEB in Tunisian families at risk. Haplotype analysis and homozygosity by descent suggest that all families classified clinically as having DEB and the patient who presented with an unclassified form of EB are likely linked to the COL7A1 gene, and showed evidence for exclusion for the simplex and junctional cases. For COL7A1 linked families, two main haplotypes were shared by eight families. For all the other cases, haplotypic heterogeneity was observed, thus suggesting a mutational heterogeneity among Tunisian DEB families. The genetic results matched with the ultrastructural analysis in all the DEB families and with the clinical examination in 94.7% of all studied DEB families. This study is to our knowledge the first genetic investigation of DEB in the Maghrebian population. We propose a selection of informative markers and show the importance of haplotype analysis as a relatively easy and cost and time effective method for carrier screening and prenatal diagnosis of DEB in consanguineous families at risk.     

Efficacité pédagogique de la simulation dans l’apprentissage du sevrage tabagique par les étudiants en sciences de santé : Revue systématique

Background: Simulation is one of the educational tools that can be used in thelearning process to help with smoking cessation. Aim: To synthesize all the publications studying the contribution of simulation as aneducational tool in the acquisition of skills to help with smoking cessation. Methods: We performed a systematic review of the Francophone and Anglophoneliterature over the past 24 years (1997 to 2020) using the PubMed, Science Direct andCochrane Library databases. Results: A total of 14 articles were included. The most used methods were thestandardized patient, role play and video projection with discussion. The simulation hasnot only proved its effectiveness in terms of acquiring knowledge and self-confidencein the management of the smoking patient in the short term, but also in the acquisitionof verbal and non-verbal skills in the long term. Conclusion: This review highlighted the interest of simulation as an educational tool toacquire skills to help with smoking cessation regardless of the method used.     

Rapid and inexpensive detection of common HBB gene mutations in Tunisian population by high-resolution melting analysis: Implication for molecular diagnosis

In Tunisia, β-thalassemia is a common hereditary disease with a carrying rate of 2.21%. Up to now, detection of responsible mutations was made by laborious, expensive, and/or time consuming methods. The aim of this study is to develop and validate a specific assay for detection of the two most frequent mutations in Tunisian population, the IVS-I-110 (G → A) and Cd39 (C → T) mutations. In this study, we optimize high resolution melting analysis (HRMA) conditions for these mutations, using control DNAs. Then, we evaluate the strength of this methodology by screening a cohort of patients with β-thalassemia. All examined reference DNA samples were unambiguously distinguished from each other. For the blinded test, the results were completely compatible with direct sequencing, performed after the HRMA. As HRMA represents a highly sensitive and high-throughput gene scanning method, it can provide timely diagnosis at low cost for effective clinical management of β-thalassemia.