SNUBH researchers identify genetic factors influencing severity of rare PAX2-related kidney and eye disease

A research team at the Seoul National University Bundang Hospital (SNUBH) demonstrated that the progression and prognosis of kidney failure and eye abnormalities in patients with the ultra-rare PAX2 gene mutation differ according to the type of genetic variant present, marking the first time this has been demonstrated globally, the hospital said Thursday.

Although kidneys and eyes are typically considered distinct organs, both develop under the influence of the PAX2 gene during fetal growth.

In a small number of individuals, mutations in PAX2 impair the formation and development of both organs, leading to a rare disorder marked by chronic kidney disease and a range of ocular issues, including nystagmus, strabismus, and visual field defects, beginning in childhood.

Until now, the reasons for the substantial variability in disease progression among affected individuals have remained unclear.

Some patients rapidly advance to end-stage renal disease and experience severe vision loss in early adolescence, while others retain relatively stable kidney and eye function into adulthood. This lack of understanding has hindered efforts to identify high-risk patients at an early stage.

To address this, the team, led by Professors Kim Ji-hyun of the Department of Pediatrics at SNUBH, Ahn Yo-han of the Department of Pediatrics at Seoul National University Children’s Hospital, and Jung Jae-ho of the Department of Ophthalmology at Seoul National University Children’s Hospital, analyzed 27 patients diagnosed with PAX2 mutations across four Korean medical centers between 2006 and 2022. The study also incorporated data from 49 previous international studies, bringing the total cohort to 328 patients.

The team’s findings revealed that patients with “truncating” mutations -- those that completely disrupt the structure of the encoded protein -- progressed to end-stage renal disease much more rapidly than those with “non-truncating” mutations, where some protein function is preserved.

Truncating mutations were also more likely to be associated with severe and early-onset eye abnormalities.

On average, patients with truncating mutations required dialysis or kidney transplantation by age 11, while those with non-truncating mutations maintained kidney function until about age 24.

Truncating mutations were also more frequently linked to papillorenal syndrome, a condition where both kidney and optic nerve abnormalities are present.

The study further established that proteinuria (seen in 37 percent of patients) and ocular symptoms (26 percent) were the most common clinical signs in PAX2 mutation carriers, providing a clearer picture of symptom prevalence than previously available.

“This research provides a crucial basis for predicting patient outcomes and setting treatment strategies based on mutation type in children suffering from kidney and eye diseases due to PAX2 mutations,” Professor Kim said. “By identifying high-risk patients—those with truncating mutations—we can pursue early diagnosis and interventions that may slow disease progression and improve quality of life.”

Professor Kim also advised that children presenting with proteinuria or unusual eye movements should promptly undergo specialized medical evaluations.

The study’s findings were published in European Journal of Human Genetics.