COQ8B gene deficiency as a potential cause of retinal abnormalities in Pediatric kidney transplant recipients

Abstract Coenzyme Q10 synthesis disorder caused by 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). Through long-term follow-up of 26 renal transplant children with COQ8B variants at our center, it is observed that, despite favorable renal transplant outcomes, 23.1% of children experienced night blindness or other ocular symptoms. 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, which was an important indicator for the early diagnosis of RP. No known RP-associated pathogenic gene mutations were identified in the WES data of these children upon screening. Transcriptome analysis suggested that the potential association between COQ8B gene mutations and RP was related to ATP synthesis, oxidative phosphorylation, and phototransduction pathways. This study was the first to propose that COQ8B gene deficiency leading to retinal disorders in kidney transplanted children is not sporadic. Coenzyme Q10 supplementation may have a protective effect on the retina after renal transplantation in children with COQ8B mutations, requiring further research and clinical attention.