Clinical and genetic study on two Chinese families with Wagner vitreoretinopathy

Wagner vitreoretinopathy (WVR) is a rare non-syndromic autosomal dominant inherited vitreoretinopathy. We studied the phenotypes of two Chinese families with WVR and identified the pathogenic variants.

Four affected individuals were involved in this study. Three of them underwent detailed ophthalmic examinations, including best-corrected visual acuity (BCVA), dilated ophthalmoscopy, optical coherence tomography (OCT), visual field testing, and electroretinograms (ERG). The DNA sample of the proband was sequenced using our customized capture panel, which includes 338 retinal disease genes. Sanger sequencing was performed for validation and segregation.

Affected subjects manifested typical WVR features, including an optically empty vitreous with vitreoretinal membranes and veils, chorioretinal atrophy, and presenile cataracts. One patient was complicated with retinal detachment. BCVA ranged from light perception to 20/33. Reduced retinal thickness, loss, or discontinuation of ellipsoid and interdigitation zone were shown by OCT. Visual field testing displayed various degrees of peripheral vision loss. ERG recorded moderate to severe decline of both rod and cone responses. Next generation sequencing (NGS) combined with segregation test revealed two splice-site pathogenic variants (c.9265 + 2 T > A and c.4004-1 G > T) in VCAN gene.

Clinical manifestations are highly variable among WVR patients. Retinal detachment is common in WVR and the most vision-threatening complication. Next generation sequencing is a useful tool in precise diagnosis of this spectrum of diseases with highly heterogeneous or overlapped phenotypes.