RS35705950 polymorphism of MUC5B Gene: Association with Rheumatoid Arthritis and Interstitial lung disease in Tunisian Population.

Introduction: Interstitial lung disease (ILD) is the most common extra-articular manifestation in rheumatoid arthritis (RA). Studies have concluded that there is an association between rs35705950 polymorphism of the MUC5B gene and RA-ILD.

Aim: To explore this polymorphism in a cohort of Tunisian patients suffering from RA with or without ILD and stufdy its association to ILD during RA.

Genetic polymorphisms in VEGFA and VEGFR2 genes associated with coronary heart disease susceptibility and severity.

Background: ​Vascular endothelial growth factor A (VEGFA) is well acknowledged as a powerful angiogenesis-promoting agent mainly through its receptor VEGFR2. Ischemia stimulates VEGFA/VEGFR2 signaling pathway and elevated serum levels of VEGFA were detected in coronary heart disease (CHD) patients. The goal of the current study is to determine how four SNPs in the genes for VEGFA (rs3025039 and rs699947) and VEGFR2 (rs2305948 and rs1870377) contribute to the development of CHD.

Case report: 7p22.3 deletion and 8q24.3 duplication in a patient with epilepsy and psychomotor delay-Does both possibly act to modulate a candidate gene region for the patient's phenotype?

Psychomotor delay, epilepsy and dysmorphic features are clinical signs which are described in multiple syndromes due to chromosomal imbalances or mutations involving key genes implicated in the stages of Early Embryonic Development. In this context, we report a 10 years old Tunisian patient with these three signs. Our objective is to determine the cause of developmental, behavioral and facial abnormalities in this patient.

The Role of Recent Admixture in Forming the Contemporary West Eurasian Genomic Landscape.

Over the past few years, studies of DNA isolated from human fossils and archaeological remains have generated considerable novel insight into the history of our species. Several landmark papers have described the genomes of ancient humans across West Eurasia, demonstrating the presence of large-scale, dynamic population movements over the last 10,000 years, such that ancestry across present-day populations is likely to be a mixture of several ancient groups [1-7]. While these efforts are bringing the details of West Eurasian prehistory into increasing focus, studies aimed at understanding the processes behind the generation of the current West Eurasian genetic landscape have been limited by the number of populations sampled or have been either too regional or global in their outlook [8-11].

Regulation of SCN5A by microRNAs: miR-219 modulates SCN5A transcript expression and the effects of flecainide intoxication in mice.

Background: The human cardiac action potential in atrial and ventricular cells is initiated by a fast-activating, fast-inactivating sodium current generated by the SCN5A/Nav1.5 channel in association with its β1/SCN1B subunit. The role of Nav1.

Molecular diagnosis of distal renal tubular acidosis in Tunisian patients: proposed algorithm for Northern Africa populations for the ATP6V1B1, ATP6V0A4 and SCL4A1 genes.

Background: Primary distal renal tubular acidosis (dRTA) caused by mutations in the genes that codify for the H + -ATPase pump subunits is a heterogeneous disease with a poor phenotype-genotype correlation. Up to now, large cohorts of dRTA Tunisian patients have not been analyzed, and molecular defects may differ from those described in other ethnicities. We aim to identify molecular defects present in the ATP6V1B1, ATP6V0A4 and SLC4A1 genes in a Tunisian cohort, according to the following algorithm: first, ATP6V1B1 gene analysis in dRTA patients with sensorineural hearing loss (SNHL) or unknown hearing status.

Relationship between GSTM1 and GSTT1 polymorphisms and schizophrenia: a case-control study in a Tunisian population.

There is substantial evidence found in the literature that supports the fact that the presence of oxidative stress may play an important role in the pathophysiology of schizophrenia. The glutathione S-transferases (GSTs) forms one of the major detoxifying groups of enzymes responsible for eliminating products of oxidative stress. Interindividual differences observed in the metabolism of xenobiotics have been attributed to the genetic polymorphism of genes coding for enzymes involved in detoxification.

Homozygous deletion of EPB41 genuine AUG-containing exons results in mRNA splicing defects, NMD activation and protein 4.1R complete deficiency in hereditary elliptocytosis.

Complete loss of protein 4.1R in red blood cell membrane is a very rare condition in humans. We here explore the third case.

Xmn I polymorphism associated with concomitant activation of Gγ and Aγ globin gene transcription on a β0-thalassemia chromosome.

The -158 (C→T) nucleotide change, known as Xmn I polymorphism, occurs in (G)γ-globin gene promoter, and results in elevated fetal hemoglobin (HbF). We found this mutation in cis of a β(0)-thalassemia splicing mutation. Despite the complete absence of adult HbA, the phenotype was only moderately severe with no detectable alteration of α-globin gene expression.

Atypical hemolytic uremic syndrome in the Tunisian population.

Background: Hemolytic uremic syndrome consists of a triad of acquired hemolytic anemia, thrombocytopenia and renal failure.

Aim: Our objectives were to determine epidemiology, clinical and laboratory characteristics of patients with atypical hemolytic uremic syndrome (aHUS) to determine the relationship between the complement protein deficit and aHUS in the Tunisian population.

Methods: We studied retrospectively four cases of atypical HUS in adults admitted in the Nephrology Department of Fattouma Bourguiba Universitary Hospital in Monastir between 2000 and 2008.

Association of GSTM1 and GSTT1 polymorphisms with chronic obstructive pulmonary disease in a Tunisian population.

GSTM1 and GSTT1 polymorphisms have been proposed in relationship with chronic obstructive pulmonary disease (COPD). We investigated the association between these polymorphisms and COPD (as well as its subtypes emphysema and chronic bronchitis) in 234 COPD patients and 182 healthy controls in the Tunisian population. Genotyping was performed using multiplex PCR.

Hemoglobinopathies in North Africa: a review.

Hemolytic anemias are very common diseases. Among these diseases, hemoglobinopathies are widely spread throughout the Mediterranean Basin, including North Africa (Tunisia, Algeria and Morocco). Their severity and disabling nature make them a major public health problem.

Rapid genotyping of alpha 1 antitrypsin deletion mutation (PI*Mmalton) using bi-directional PCR allele-specific amplification.

Alpha 1 antitrypsin deficiency (AATD) is a well recognized genetic risk factor for pulmonary disease and less common liver disease. The two most common deficiency alleles worldwide PI*S and PI*Z can be easily detected using several molecular methods. However, there are at least 30 other AATD variants, which are only detectable by alpha 1 antitrypsin (AAT) gene sequencing and, therefore, seem to be more under-recognized than the PI*S and PI*Z alleles.

Cryptic splicing sites are differentially utilized in vivo.

It has long been considered that cryptic splice sites are ignored by the splicing machinery in the context of intact genuine splice sites. In the present study, it is shown that cryptic splice sites are utilized in all circumstances, when the authentic site is intact, partially functional or completely abolished. Their use would therefore contribute to a background lack of fidelity in the context of the wild-type sequence.

Clinical and molecular aspects of haemoglobinopathies in Tunisia.

Background: For the last two decades, studies on the population genetics of Tunisians have focused on variations of protein and genetic markers. Results confirmed the genetic heterogeneity of Tunisians caused by the admixtures with migratory human groups arriving mainly from Africa, Europe, and Asia. These studies also allowed the screening of rare mutants and many haemoglobin variants.

Oxidant, antioxidant status and metabolic data in patients with beta-thalassemia.

Background: In beta-thalassemia major impaired biosynthesis of beta globin leads to accumulation of unpaired alpha globin chain. An iron overload, usually observed, generates oxygen-free radicals and peroxidative tissue injury.

Aim: To investigate hematological parameters, oxidative stress and the antioxidant capacity in beta-thalassemia patients compared to control subjects in order to determine their impact in several organs functions.