F. Khalsi

Association of M470V polymorphism of CFTR gene with variability of clinical expression of asthma: Case-report study

INTRODUCTION AND OBJECTIVES Asthma is a complex genetic disorder. Several genes have been found associated with asthma. The cystic fibrosis transmembrane conductance regulator (CFTR) gene is one of them. The aim of this study was to perform a comparative analysis of the genotype and allele frequency distributions of the biallelic marker M470V within the CFTR gene on mutant and wide chromosomes. PATIENTS AND METHODS The molecular approach consists in the genotyping of the M470V marker by the PCR-RFLP technique in 105 asthmatic patients, aged between four months and 17 years, and 105 healthy subjects. RESULTS We found a significant difference in the genotype frequencies between the two studied groups (χ2=9.855, P=0.007). The V/V genotype was over represented in the asthmatic group as compared to the controls (32.38% vs. 16.19%). Whereas, the M/V genotype is more frequent in healthy subjects (40.95% vs. 28.71%). We also noted a significant difference in allelic distribution of M470V with associated diseases (χ2=9.610, P=0.022). CONCLUSIONS The present study is the first report on the distribution of the M470V polymorphism in asthmatic Tunisian patients. We noticed that the M470V variant could modulate the clinical phenotype of asthmatic patients. This preliminary study will establish the molecular basis of this disease in Tunisia.

Rabies encephalitis in children: a resurgence of a fatal anthropozoonosis

Rabies is a ubiquitous fatal disease and its large wild life reservoir may precipitate a flare-up whenever stringent control is relaxed. It remains a serious public health challenge in the developing world. It is estimated that up to 40–60,000 cases of human rabies occur annually, mostly in rural areas of Africa and Asia, and with a particularly high incidence in young children (under the age of 15 years). Although Tunisia has implemented a national program against rabies since 1982, we are still recording one or two cases every year; in these cases, the victims generally did not consult after a dog bite and did not receive prophylaxis. We report in this article the case of an eleven year old child, who received post exposure prophylaxis and unfortunately developed fatal rabies.

Cystic fibrosis in Tunisian children: a review of 32 children

Background Cystic fibrosis is rare in Tunisia. Its diagnosis requires experienced specialists. Its prognosis is poor in developing countries. Objectives To study the epidemiologic, clinical, genetic features and the therapeutic challenges of cystic fibrosis in Tunisian children. Methods Covering a period of 21 years, this retrospective study included all patients with a definite diagnosis of cystic fibrosis from the Pediatrics Department B of The Childrens Hospital of Tunis. Results Data from 32 children (14 boys and 18 girls) were collected. The diagnosis was made during the first year of life in 28 cases. Meconium ileus was found in 5 cases, respiratory manifestations in 22 cases, chronic diarrhea in 19 cases, faltering growth in 17 cases and a pseudo Barter syndrome in 2 cases. The sweat chloride test was positive in all cases. The most frequent mutation was F508del (56% of cases). Respiratory complications marked the outcome. Among our 32 patients, 15 patients (50%) died at an average age of 5 years and 3 months, mainly due to respiratory failure. The mean age of the surviving patients was 5 years. Conclusion Cystic fibrosis prognosis is poor in our series compared to developed countries due to the longer diagnostic delay and the limited therapeutic options.

Le syndrome de pseudo-Bartter comme seule manifestation de mucoviscidose chez un enfant porteur de la mutation 711+1 G>T/IVS8-5T : un nouveau visage d’une ancienne maladie

Pseudo-Bartter syndrome (PBS) describes an uncommon complication of cystic fibrosis leading to hypochloraemic, hypokalaemic metabolic alkalosis. PBS as the sole manifestation of cystic fibrosis in children is extremely rare and has never been described in patients carrying 5T variant. We report a clinical, biochemical and genetic study of a four year-old boy presenting a pseudo-Bartter syndrome as the sole manifestation of cystic fibrosis. All 27 exons and the flanking intron regions of the CFTR gene were analysed by PCR and direct sequencing. Direct sequencing was also used to analyse TGmTn and M470V polymorphisms in the patient and his parents. Two sweat tests were abnormal with elevated chloride levels at 78 and 88 mmol/L. DNA sequencing revealed a heterozygous mutation 711+1 G>T and an IVS8-T5 allele. The mutation 711+1 G>T is in trans with the IVS8-T5-TG11 allele and the child carried M470/V470 genotype. To the best of our knowledge, the genotype 711+1 G>T /IVS8-5T found in our patient is described for the first time. The role of TG11-5T-V470 allele in cases of cystic fibrosis with PB syndrome remains to be determined.

SFP PC-43 - Méningo-encéphalite à West Nile Virus chez le nouveau-né : A propos d’un cas

Introduction L’infection par le West Nile Virus (WNV) est une arbovirose rare. Elle evolue par epidemies au Maghreb. Chez l’enfant, elle est benigne dans la quasi-totalite des cas. L’atteinte neurologique est rarement observee. Nous rapportons l’observation d’un nouveau-ne hospitalise pour une meningo-encephalite a WNV. Observation Moemen, âge de 23 jours, a ete hospitalise pour un etat de mal convulsif fait de clonies hemicorporelles gauches ayant dure 4 heures dans un contexte febrile. Ces convulsions ont cede sous phenobarbital sans recidive. A la biologie, absence de syndrome inflammatoire. La PL a montre une pleiocytose a 74 /mm 3 (100% lymphocytes), une hperalbuminorrachie, une normoglucorrachie et une culture negative. L’IRM cerebrale a revele des anomalies de signal de la substance blanche cerebelleuse et bi thalamique. Le diagnostic de meningo-encephalite virale a ete retenu. L’etude PCR herpes et enterovirus dans le LCR etait negative. La serologie WNV dans le LCR etait positive a IgM. L’evolution clinique a ete favorable avec un recul evolutif de 3 mois. Conclusion La forme neuro-invasive de l’infection a WNV chez le nouveau- ne est tres rare. Le traitement est symptomatique. Son pronostic immediat semble favorable, cependant les sequelles ulterieures restent a determiner.