0000000000281255
AUTHOR
Vincent Lhussiez
Cohen Syndrome-Associated Cataract Is Explained by VPS13B Functions in Lens Homeostasis and Is Modified by Additional Genetic Factors
International audience; Purpose: Cohen syndrome (CS) is a rare genetic disorder caused by variants of the VPS13B gene. CS patients are affected with a severe form of retinal dystrophy, and in several cases cataracts also develop. The purpose of this study was to investigate the mechanisms and risk factors for cataract in CS, as well as to report on cataract surgeries in CS patients.Methods: To understand how VPS13B is associated with visual impairments in CS, we generated the Vps13b∆Ex3/∆Ex3 mouse model. Mice from 1 to 3 months of age were followed by ophthalmoscopy and slit-lamp examinations. Phenotypes were investigated by histology, immunohistochemistry, and western blot. Literature anal…
Caractérisation des effets ophtalmiques du syndrome de Cohen chez des souris VPS13B-/- et identification des mécanismes moléculaires impliqué dans la pathogenèse.
Cohen Syndrome (CS) is a rare autosomal recessive disease caused by variations in the gene coding for the vacuolar tri-vacuolar protein 13B (VPS13B or COH1). CS patients have common features including typical facial appearance, neutropenia, abnormal trunk fat distribution, microcephaly, myopia and retinal damage. My thesis project aimed to characterize the ophthalmologic phenotype of a mouse model Vps13bEx3/Ex3 to determine the molecular mechanisms involved in the development of CS retinopathy.First, we showed that Vps13bEx3/Ex3 mice develop a cataract between 2 and 3 months. Disorganization of the fibrous cells of the crystalline lens and their differentiation into mesenchymal cells were o…