Analysis of CLCNKB mutations at dimer‐interface,calcium‐binding site,and pore reveals a variety of functional alterations in ClC‐Kb channel leading to Bartter syndrome

Pathological missense mutations in CLCNKB gene give a wide spectrum of clinical phenotypes in Bartter syndrome type III patients. Molecular analysis of the mutated ClC‐Kb channels can be helpful to classify the mutations according to their functional alteration. We investigated the functional consequences of nine mutations in the CLCNKB gene causing Bartter syndrome. We first established that all tested mutations lead to decreased ClC‐Kb currents. Combining electrophysiological and biochemical methods in Xenopus laevis oocytes and in MDCKII cells, we identified three classes of mutations. One class is characterized by altered channel trafficking. p.A210V, p.P216L, p.G424R, and p.G437R are totally or partially retained in the endoplasmic reticulum. p.S218N is characterized by reduced channel insertion at the plasma membrane and altered pH‐sensitivity; thus, it falls in the second class of mutations. Finally, we found a novel class of functionally inactivated mutants normally present at the plasma membrane. Indeed, we found that p.A204T alters the pH‐sensitivity, p.A254V abolishes the calcium‐sensitivity. p.G219C and p.G465R are probably partially inactive at the plasma membrane. In conclusion, most pathogenic mutants accumulate partly or totally in intracellular compartments, but some mutants are normally present at the membrane surface and simultaneously show a large range of altered channel gating properties.     

Watering of the eyes in infants: how to treat it?

The congenital impermeability of see lacrymal is frequent affection of new born. Whimpering is the master symptom. We propose a retrospective study with 492 cases of congenital imperforations treated in our ophthalmology department in Sfax, between 1990 and 2000. We showed the clinical characteristics of our study and therapeutic result. For these children, various therapeutic methods were used: the washing of the lacrymal ways with or without pressure. A survey is undertaken on first, second and third time if necessary; in the event of failure we do lacrymal pathway intubation or the dacryocystorhinostomy at a more advanced age. The naso-lacrymal repermeability is obtained in 92.9% (457 cases), spontaneous repermeabilisation in 112 cases; 84 cases by washing and 293 cases by single or multiple survey. This study is encouraging collaboration between pediatrics and ophthalmologists to consult early when whimpering is noted.     

Persistent forms of cow's milk allergy. Report of 6 cases

BACKGROUND: Cow's milk allergy is defined as reproducible adverse reaction to a food protein antigen which is immune medieted. About 80 to 90 % become clinically tolerated within the first three year of live. The aim of this study is to evaluate the clinical, immunological and evolutive characteristics of the 10 % to 20 % of persistent form of cow's milk allergy. METHODS: This study included six persistent form of cow's milk allergy (2 boys and 4 girls). The provocation challenge test according to Rance recommendation, have been made from 6 months to one year. RESULTS: 4/6 infants with persistent cow's milk allergy have an atopic familial disease. Clinical presentation changed over time at once symptoms were preventely gastrointestinal, at the end there was an increased frequency of atopic disease (asthma: 4/6 infants) CONCLUSION: Persistent form of cow's milk allergy are characterized by considerable importance of familial atopic disease; change in cow's milk allergy manifestations over time and more prolonged delay between cow's milk persistent consumption and manifestations of symptoms.