Introduction: COQ8B gene deficiency is among the most prevalent causes of end-stage renal disease (ESRD) in children, which usually presents as isolated kidney disease, with sporadic cases associated with extrarenal symptoms such as retinitis pigmentosa (RP).
Methods: The clinical data of children with COQ8B gene mutations who underwent renal transplantation in our center from January 2013 to December 2024 were retrospectively analyzed, and the renal allograft and ocular prognosis information were collected. Children were recruited for detailed ophthalmic examinations such as fundus photography, electroretinogram (ERG), visual acuity, and visual field. Pediatric transplant recipients without COQ8B gene mutations were included as controls. Children 's whole exome sequencing data were screened for known RP-related genes. Additionally, transcriptomic data from public databases were analyzed to explore the potential mechanisms underlying retinal abnormalities caused by COQ8B gene deficiency.
Results: A total of 26 renal transplant recipients with COQ8B gene mutations were included. Despite the fine long-term prognosis of the transplanted kidney, night blindness or other ocular symptoms developed in six (23.1%) patients during follow-up. Nine children were recruited for systematic ophthalmic examination and found that three of them were definitely diagnosed with RP, and the remaining children had varying degrees of retinal abnormalities regardless of perceived ocular discomfort.

Compared with kidney transplant children without this genetic variant, children with the COQ8B genetic variant had significantly worse ERG results. The amplitude of the b-wave was decreased (22.30±9.04 vs 35.65±10.96, P=0.03) and the latency was prolonged (39.24±5.51 vs 34.10±2.26, P<0.01) in dark adaptation. No known RP-associated pathogenic gene mutations were identified in the WES data of these children upon screening. Transcriptome enrichment analysis suggests that the potential association between COQ8B gene mutations and RP is related to ATP synthesis, oxidative phosphorylation, and phototransduction pathways.

Conclusions: Although the prognosis of allografts in children with COQ8B gene mutations is favorable, retinal abnormalities may develop and even progress to RP during long-term follow-up. The pathogenic mechanism may be associated with impaired ATP synthesis, more severe oxidative stress damage, and photoconduction abnormality in rods in the retina due to defective coenzyme Q10 synthesis. Coenzyme Q10 supplementation may have a protective effect on the retina after renal transplantation in children with COQ8B mutations.