Bi-Allelic Pathogenic Variations in Including Deletions Are Associated with an Early Onset Progressive Form of Retinitis Pigmentosa.

Bi-allelic pathogenic variants in cause retinitis pigmentosa (RP). Since deletions of more than one exon have been reported repeatedly for , CNV (copy number variation) analysis of next-generation sequencing (NGS) data has proven important in molecular genetic diagnostics of . CNV analysis was performed on NGS data of 677 individuals with inherited retinal diseases (IRD) and confirmed by quantitative RT-PCR analysis. Clinical evaluation was based on retrospective records. Clinical re-examination included visual field examination, dark adaption, scotopic and photopic full-field electroretinograms (ffERG), multifocal ERG (mfERG) and optic coherence tomography (OCT). Fourteen variants were detected in in six individuals, three of which were deletions of more than one exon. Clinical examinations of five out of six individuals revealed a severe phenotype with early-onset generalized retinal dystrophy with night blindness and progressive visual field loss; however, one individual had a milder phenotype. Three individuals had hearing impairments. We show that deletions represent a substantial part of the causative variants in and emphasize that CNV analysis should be included in the molecular genetic diagnostics of IRDs.