Zéro de conduite: déficience intellectuelle et comportement excessif : comment agir ?

Ce travail porte sur l’exploration des stratégies d’accompagnement des personnes ayant une déficience intellectuelle et présentant un comportement excessif. Il met en lumière le cheminement permettant au MSP d’appliquer « l’approche positive de la personne » selon Denise Fraser et Lucien Labbé. Non seulement cette recherche donne des éléments pour analyser des situations problématiques, mais elle apporte des stratégies d’intervention. L’accent est mis sur l’attitude que le professionnel peut adopter afin de faire évoluer un processus de réciprocité et d’interdépendance avec la personne. La posture professionnelle empruntée par l’intervenant lui permettra de se positionner et de rediriger la personne vers des alternatives positives pour gérer sa vie

Defective signaling through plexin-A1 compromises the development of the peripheral olfactory system and neuroendocrine reproductive axis in mice

The olfacto-genital syndrome (Kallmann syndrome) associates congenital hypogonadism due to gonadotropin-releasing hormone (GnRH) deficiency and anosmia. This is a genetically heterogeneous developmental disease with various modes of transmission, including oligogenic inheritance. Previous reports have involved defective cell signaling by semaphorin-3A in the disease pathogenesis. Here, we report that the embryonic phenotype of Plxna1-/- mutant mice lacking plexin-A1 (a major receptor of class 3 semaphorins), though not fully penetrant, resembles that of Kallmann syndrome fetuses. Pathohistological analysis indeed showed a strongly abnormal development of the peripheral olfactory system and defective embryonic migration of the neuroendocrine GnRH cells to the hypothalamic brain region in some of the mutant mice, which resulted in reduced fertility in adult males. We thus screened 250 patients for the presence of mutations in PLXNA1, and identified different nonsynonymous mutations (p.V349L, p.V437L, p.R528W, p.H684Y, p.G720E, p.R740H, p.R813H, p.R840Q, p.A854T, p.R897H, p.L1464V, p.K1618T, p.C1744F), all at heterozygous state, in 15 patients. Most of these mutations are predicted to affect plexin-A1 stability or signaling activity based on predictive algorithms and a structural model of the protein. Moreover, in vitro experiments allowed us to show the existence of deleterious effects of eight mutations (including a transcript splicing defect), none of which are expected to result in a complete loss of protein synthesis, targeting, or signaling activity, though. Our findings indicate that signaling insufficiency through plexin-A1 can contribute to the pathogenesis of Kallmann syndrome, and further substantiate the oligogenic pattern of inheritance in this developmental disorder