L’utilisation de séquençage de l’exome, appliqué à l’étude des maladies rares, a permis à notre équipe d’identifier 4 gènes responsables d’OAVS : MYT1, précédemment rapporté, et ZYG11B,
ZIC3 et EYA3, tous 3 faisant l’objet de ce travail. Dans chacun des cas, des analyses
complémentaires par séquençage du génome, ou études fonctionnelles sur modèle cellulaire ou animal, ont été nécessaires pour apporter la preuve de leur implication.
Si cette stratégie a été appliquée avec succès, ces limites nous imposent de trouver de nouveaux outils pour décrypter les mécanismes moléculaires impliqués dans l’OAVS. Parmi ceux-ci, l’intégration de technologies OMICs, l’identification de cibles après exposition toxique sur modèle animal, et l’utilisation de méthodes statistiques appliquées aux analyses génomiques semblent les plus pertinents. Néanmoins, une meilleure définition clinique de l’OAVS, basée sur des critères objectifs et faisant intervenir des techniques d’imagerie médicale, est un
177 préalable indispensable à ces investigations biologiques. Notre équipe a été identifiée comme experte pour l’OAVS, au sein du projet européen Solve-RD, auquel nous participons au titre de l’ERN-ITHACA. Ce travail en réseau, permettant de bénéficier de la meilleure expertise dans les domaines cliniques et biologiques à l’échelle européenne, est à même d’offrir les conditions pour aboutir à ces perspectives dans l’OAVS.
178
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