SARS-CoV-2 Nasopharyngeal Swab Testing-False-Negative Results From a Pervasive Anatomical Misconception.

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 analysis was performed to determine specific characteristic features of cataract in CS and to identify potential genotype-phenotype correlations.

RESULTS

Cataracts rapidly developed in 2-month-old knockout mice and were present in almost all lenses at 3 months. Eye fundi appeared normal until cataract development. Lens immunostaining revealed that cataract formation was associated with the appearance of large vacuoles in the cortical area, epithelial-mesenchymal transition, and fibrosis. In later stages, cataracts became hypermature, leading to profound retinal remodeling due to inflammatory events. Literature analysis showed that CS-related cataracts display specific features compared to other forms of retinitis pigmentosa-related cataracts, and their onset is modified by additional genetic factors. Corroboratively, we were able to isolate a subline of the Vps13b∆Ex3/∆Ex3 model with delayed cataract onset.

CONCLUSIONS

VPS13B participates in lens homeostasis, and the CS-related cataract development dynamic is linked to additional genetic factors.