VSX2 variants are responsible for bipolar cell dysfunction with distinct lens and chorioretinal alterations.

Abstract

Purpose : Congenital stationary night blindness (CSNB) is a group of genetically and clinically heterogeneous retinal disorders, usually manifesting with infantile nystagmus, reduced visual acuity, variable degree of myopia and poor visual behavior in dim light. The diagnosis is done on the basis of full-field electroretinogram (ffERG) features. Most of the patients are characterized by an electronegative Schubert-Bornschein-type of ffERG, showing either a signal transmission defect from photoreceptor to all bipolar cells (incomplete (ic)CSNB) or selectively affecting rod and cone ON-bipolar cells (complete (c)CSNB). The goal of this study was to identify the gene defect in a family with non-syndromic CSNB with peculiar characteristics.

Methods : Three patients from two unrelated families have been clinically and genetically explored by state-of-the-art methods.

Results : Patients had infantile nystagmus, low stable visual acuity, myopia and night blindness. Two older patients had bilateral lens luxation and underwent lens extraction. All patients presented atrophic peripheral chorioretinal changes. The ffERG revealed an electronegative Schubert-Bornschein appearance, but combining characteristics of incomplete and complete CSNB, affecting rod and cone ON- and OFF-bipolar cells. Whole exome and Sanger sequencing identified in each index case a novel homozygous variant (respectively c.595C>T p.(Arg199Cys) and c.698C>T p.(Pro233Leu)) in VSX2 co-segregating with the phenotype in available family members.

Conclusions : Variants in VSX2 can lead to different phenotypes, either defects of early ocular development (anophthalmia, microphthalmia and coloboma) or peculiar CSNB with lens luxation and chorioretinal changes, described herein. VSX2 is a major regulator of early ocular development and is highly expressed in bipolar cells in adult retina. Further studies are needed to understand the pathogenic mechanisms associated with variants in VSX2 leading to two distinct phenotypes.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.