Isolated and syndromic retinal degeneration associated with POC5 variants.

Abstract

Purpose : Biallelic gene defect in POC5 have been recently reported in association with syndromic rod-cone degeneration in one patient. Systemic findings included low weight, short stature, microcephaly and recurrent glomerulonephritis. The purpose of this study was to report a detailed phenotypic description of French patients harboring POC5 pathogenic variants.

Methods : Patients harboring gene defects in POC5 were retrieved from cohorts of Inherited Retinal Degeneration (IRD) followed at the Exploration de la Vision et Neuro-Ophtalmologie, CHU de Lille and at the National Reference Center for rare ocular diseases of Quinze-Vingts hospital, Paris. Best corrected visual acuity, slit-lamp examination, perimetry, full field electroretinography (ffERG) and multimodal imaging including color photos, infrared reflectane, short-wave autofluorescence and optical coherence tomography were performed for all patients. Past medical history was also collected. POC5 variants were identified through customized IRD multigene Next-Generation Sequencing panels. Variant confirmation and co-segregation were performed by direct Sanger sequencing.

Results : Three patients from two unrelated families were selected. The first patient from a consanguineous Algerian family presented infantile nystagmus and low vision from birth. She had been diagnosed with syndromic severe early-onset rod-cone retinal degeneration. Systemic findings included low weight and short stature, insulin-dependent diabetes, glomerular nephropathy, cirrhosis and primary amenorrhea. Two sibs from a second unrelated French family had been referred in their teen age for night blindness and progressive visual loss. They presented a rod-cone retinal degeneration complicated by posterior subcapsular cataracts. Interestingly, ffERG was of cone-dominated type in the younger patient. Systemic evaluation for liver and kidney disease was performed and revealed no abnormalities. Patients from both families harbored novel homozygous loss-of-function pathogenic variants in POC5.

Conclusions : Biallelic pathogenic variants in POC5 can be associated with both isolated and syndromic severe rod-cone degeneration. Systemic evaluation for diabetes, liver and kidney disease should be performed if POC5 gene defects are identified in IRD patients.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

 

Ultra wide field short wave fundus autofluorescence.