Targeted Ngs: An Effective Approach For Molecular Diagnosis Of Hereditary Vitreoretinopathies

SummaryHereditary vitreoretinopathies (VRPs), traditionally divided into the groups of exudative and degenerative VRPs, encompass a number of diseases affecting the vitreous and the retina. These disorders are the commonest cause of inherited retinal detachment with high risk of vision loss during infancy. We designed a next generation sequencing (NGS) assay including ATOH7, COL2A1, COL9A1, COL9A2, COL9A3, COL11A1, COL18A1, FZD4, KCNJ13, KIF11, LOXL3, LRP5, NDP, TSPAN12, VCAN and ZNF408 allowing an exhaustive genetic screening with the most frequently mutated genes reported to be associated with all inherited VRPs. The diagnostic performance of this new design was evaluated on a cohort of 166 probands with a suspected clinical diagnosis of exudative or degenerative VRPs comprising 47% of children under 15 years old. We identified a large spectrum of causative mutations (single nucleotide changes as well as copy number variants) diagnosing molecular defects for 60% of the patients. Our NGS panel is therefore a promising screening method to be used efficiently in routine practice, able to detect a higher number of molecular defects than Sanger sequencing, improving significantly the molecular diagnosis of inherited VRPs.