von Willebrand factor A domain containing 8 (VWA8)- associated retinitis pigmentosa: description of a novel case and expansion of the phenotype.

PURPOSE: Retinitis pigmentosa, the most common type of inherited retinal dystrophy, is known to have great genetic heterogeneity, as pathogenic variants in approximately 100 genes have been recognized as causative. In the last decade, wide application of next-generation DNA sequencing has allowed identification of pathogenic variants in novel retinal dystrophies genes. Recently, a pathogenic variant in von Willebrand factor A domain containing protein 8 (VWA8) gene, was demonstrated to segregate in a large Chinese family with autosomal dominant (AD) retinitis pigmentosa. The current study describes the clinical and molecular characteristics of a novel retinitis pigmentosa patient carrying a pathogenic variant in the VWA8 gene.

METHODS

Ophthalmic examination, fundus photography, autofluorescence, spectral-domain optical coherence tomography, Goldmann perimetry, Full Field Stimulus Threshold (FST), full-field electroretinogram, and chromatic perimetry testing were carried out. Peripheral blood DNA was isolated, and whole exome sequencing was performed in the index case. Bioinformatic analysis was performed for the identification of the pathogenic causal variant. Analysis of the candidate variant in first-degree relatives by Sanger DNA sequencing was also performed.

RESULTS

A Mexican patient suffering from retinitis pigmentosa and her first-degree relatives were included. Classical features of retinal dystrophy were identified, including nyctalopia, peripheral visual field loss, as well as vascular attenuation, and bone spicules on fundus examination. Genetic analysis identified a novel pathogenic c.3069C > G (p.Tyr1023Ter) heterozygous VWA8 variant. Additionally, optic nerve drusen were identified, a feature not described in the family previously reported in literature.

CONCLUSION

Our results confirm VWA8 as a retinitis pigmentosa-associated gene and contributes to the phenotypic expansion of the disorder.