A 3-base pair deletion,c.9711_9713del,in DMD results in intellectual disability without muscular dystrophy

We have identified a deletion of 3 base pairs in the dystrophin gene (DMD), c.9711_9713del, in a family with nonspecific X-linked intellectual disability (ID) by sequencing of the exons of 86 known X-linked ID genes. This in-frame deletion results in the deletion of a single-amino-acid residue, Leu3238, in the brain-specific isoform Dp71 of dystrophin. Linkage analysis supported causality as the mutation was present in the 7.6 cM linkage interval on Xp22.11–Xp21.1 with a maximum positive LOD score of 2.41 (MRX85 locus). Molecular modeling predicts that the p.(Leu3238del) deletion results in the destabilization of the C-terminal domain of dystrophin and hence reduces the ability to interact with β-dystroglycan. Correspondingly, Dp71 protein levels in lymphoblastoid cells from the index patient are 6.7-fold lower than those in control cell lines (P=0.08). Subsequent determination of the creatine kinase levels in blood of the index patient showed a mild but significant elevation in serum creatine kinase, which is in line with impaired dystrophin function. In conclusion, we have identified the first DMD mutation in Dp71 that results in ID without muscular dystrophy.     

Presence of a mobilizable intracellular pool of hepatocyte growth factor in human polymorphonuclear neutrophils

Hepatocyte growth factor (HGF), a heparin-binding factor, is synthesized as a single-chain inactive precursor (pro-HGF), which is converted by proteolysis to an active heterodimer (mature HGF). HGF has pleiotropic activities and has been implicated in the regulation of mitogenesis, motogenesis, and morphogenesis of epithelial and endothelial cells. As polymorphonuclear neutrophils (PMNs) secrete numerous cytokines involved in the modulation of local inflammation, we investigated their ability to produce HGF. We found that HGF was stored in secretory vesicles and in gelatinase/specific granules. This intracellular stock was rapidly mobilized by degranulation when neutrophils were stimulated with phorbol myristate acetate or N-formylmethionyl-leucyl-phenylalanine. Cycloheximide did not affect the release of HGF. Moreover, HGF messenger RNA and protein expression was found in bone marrow myeloid cells, suggesting that HGF synthesis likely occurs during PMN maturation. In mature circulating PMNs, intracellular HGF was in the pro-HGF form, whereas the HGF secreted by degranulation was the mature form. Furthermore, PMNs pretreated with diisopropyl fluorophosphate only released the pro-HGF form, suggesting that PMN-derived serine protease(s) are involved in the proteolytic process. We also obtained evidence that secreted mature HGF binds PMN-derived glycosaminoglycans (probably heparan sulfate). These findings suggest that PMNs infiltrating damaged tissues may modulate local wound healing and repair through the production of HGF, a major mediator of tissue regeneration.     

IL-17A and IL-17F genes variants and susceptibility to childhood asthma in Tunisia

Objectives: IL-17A and IL-17F are new pro-inflammatory cytokines implicated in neutrophilic inflammation and thus, involved in the pathogenesis of asthma. We investigated the possible association among asthma and IL-17A -197G/A (rs2275913), IL-17F 7488A/G (rs763780) and IL-17F 7383A/G (rs2397084).

Methods: The study was performed in 171 patients with asthma (mean age 9.5?years, 105 boys, and 66 girls) and 171 healthy individuals matched with patients in age and sex. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to detect genes’ polymorphisms.

Results: IL-17A -197G/A and IL-17F 7383A/G were associated with asthma in children (p?=?0.008, p?=?0.001, respectively). No association was found with IL-17F 7488A/G polymorphism. Haplotype analysis revealed a significant association between GA and AG haplotypes and asthma (p?=?0.004, p?=?0.02). When patients were stratified according to the atopic status, no significant association was detected with any of the three studied variants.

Conclusion: Our results suggested that SNPs in IL-17A and IL-17F confer susceptibility to childhood asthma in Tunisia.     

Asthme du petit enfant : facteurs prédictifs de sévérité et de persistance Analyse de 180 observations

Background : Asthma is the most common chronic disease in infants. In young children, asthma still raises many questions and many points are still being debated. Aim : The aim of this study is to identifies, in asthmatic children, factors predictors of severity and persistence of symptoms. Methods: A retrospective study of asthmatic infants<3 years enrolled in the pediatric department of Sfax over a period of 5 years (2007-2011). We were interested to social and environmental factors, the allergic background, clinical severity of the disease, results of allergic skin tests, treatment and respiratory outcome.Results: We collected 180 children with a sex ratio of 2.2. Family history of atopy and exposition to passive tobacco were noted in 45 % and 52% of cases respectively. The mean age of onset of wheezing was 6.6 months. Skin tests were positives in 32% of cases. At the time of diagnosis, asthma was classified intermittent (21%), mild to moderate (55.6%) and severe (22.2%). Inhaled corticosteroids was initiated in 142 infants (78.8%). Skin tests performed in 84 patients, were positive in 32%. Factors associated with severe asthma were passive smoking, early age of onset, number of hospitalizations for exacerbation and existence of an aggravating factor.Factors predictors of persistence were an early age of onset, caesarean delivery, passive smoking and positive skin tests. Conclusion : Factors associated with persistence of asthma at the individual level remains uncertain. However, atopy and passive smoking are major indicators.     

Splenic arteriovenous fistula and portal hypertension. A case report

The authors report a rare case of portal hypertension following to an arteriovenous fistula. The embolisation of the fistula permitted to treat portal hypertension and liver histologic alterations.     

Abdomino-pelvic actinomycosis: a case report

The actinomycosis is a chronic suppurative granulomatosis disease. It is owed to a bacillus gram positive; actinomycès israelli. The cervical and thoracic localizations are most frequent. The digestive localization represents 20% of cases. It interest very rarely the pelvis and the genital tracts. We bring back the observation of a patient old of 30 years admitted for mass abdominal. To the exam, the patient had a sensibility of the left hypochondriac area and we found a mass of 6 cm of diameter. To the rectal touch, we found a mass in the bag of Douglas. The echography and the computed tomography revealed a collection under the spleen and a pelvic collection. A rectotomy is performed. The bacteriological study isolates actinomycès israelli. The collection under the spleen is drained under radiological control. Actinomycès israelli is also recovered in the pus brought back by the puncture. The patient is treated by Penicillin. The patient had a favourable evolution. No etiology is found at this patient. For this observation, the collection was accessible to a drainage permitting the diagnosis and the treatment of the actinomycosis while avoiding a mutilated surgery.