Pseudodominant Inheritance of Retinitis Pigmentosa Due to Mutations in the Phosphodiesterase 6B Gene: A Case Report

Abstract

Mutations in the phosphodiesterase 6B (PDE6B) gene are a rare cause of autosomal recessive retinitis pigmentosa (arRP). We report on a non-consanguineous family with a pseudodominant inheritance of RP due to PDE6B mutations. We conducted a chart review of four members of a Puerto Rican family who underwent a comprehensive ophthalmic evaluation by at least one of the authors. The mutational screening was done using a genotyping microarray provided by Invitae Corporation, using next-generation sequencing (NGS) technology. Genomic DNA obtained from saliva samples is enriched for targeted regions using a hybridization-based protocol and sequenced using Illumina technology. A descriptive analysis was done. Patient 1A had a normal ophthalmic examination and a heterozygous pathogenic variant in the PDE6B gene c.1540del PLeu514Trpfs*61. Patients 1B, 2A, and 2B had mid-peripheral retinitis pigmentosa, concentric visual field ring scotomata in both eyes (OU), extinguished electroretinogram (ERG), and homozygous pathogenic variants in the PDE6B gene c.1540del PLeu514Trpfs*61. Even though mutations in the PDE6B gene usually lead to arRP, they may be inherited in a pseudodominant pattern in geographically isolated populations. Genotyping studies in patients with RP are warranted to classify inheritance mode correctly.

Pseudodominant inheritance of retinitis pigmentosa in a family with mutations in the Eyes Shut Homolog (EYS) gene

“…[3][4][5] Furthermore, several RP cases with mitochondrial inheritance, digenic mutations and/or pseudodominant transmission have been hitherto reported. [6][7][8][9][10][11][12] In the last years, pseudodominant pedigrees have been uncovered mainly assessing the female symptomatic carriers of X-linked RP, [8-10] and, to lesser extent, families with autosomal recessive RP (arRP) [11][12][13] despite this is the most prevalent form of IRD worldwide. [4,5] In particular, the Eyes Shut Homolog (EYS) is the largest gene expressed in the human retina spanning over 2000 bp within the RP25 locus (6q12.1-6q15), and its sequence variants are extremely frequent causes of arRP.…”