World's first study to analyze prognosis by mutation type in PAX2 gene mutations lays foundation for precision diagnosis
A research team led by Professor Jihyun Kim from the Department of Pediatrics at Seoul National University Bundang Hospital (in collaboration with Professor Yohan Ahn from Seoul National University Hospital's Department of Pediatrics and Professor Jae Ho Jung from the Department of Ophthalmology) has announced the world’s first findings showing that the prognosis of patients with the ultra-rare "PAX2 gene mutation" significantly varies depending on the specific type of mutation.
Although the kidneys and eyes are typically regarded as entirely separate organs, both are influenced during fetal development by the same gene, PAX2. In rare cases, mutations in this gene can disrupt the development of both organs, leading to a rare congenital disorder. Affected children may suffer from chronic kidney disease starting at a young age, along with ophthalmic issues such as nystagmus, strabismus, and visual field defects.
Even among patients with PAX2 gene mutations, the progression and severity of symptoms vary widely. Some individuals may develop end-stage renal disease in early adolescence, accompanied by severe visual impairments. In contrast, others may retain relatively stable kidney and eye function into adulthood.
Until now, the cause behind such variations remained unclear, posing challenges in identifying high-risk groups who require early intervention.
To address this gap, the research team analyzed 27 patients diagnosed with PAX2 gene mutations across four institutions in Korea between 2006 and 2022. Additionally, they reviewed data from 49 previously published studies, culminating in a comprehensive analysis of 328 patients.
Their findings revealed, for the first time globally, that "truncating" mutations—those that result in a complete loss of the gene's protein structure—are associated with faster progression to end-stage renal disease and a higher likelihood of accompanying eye abnormalities, compared to "non-truncating" mutations that preserve partial protein function.
According to the study, patients with truncating mutations required dialysis or kidney transplantation at an average age of 11, whereas those with non-truncating mutations retained kidney function until around age 24. Furthermore, truncating mutation patients more frequently exhibited severe eye abnormalities at younger ages and were more likely to be diagnosed with Papillorenal Syndrome, a condition characterized by concurrent kidney and optic nerve malformations.
The researchers also found that among all clinical manifestations, proteinuria (37%) and ophthalmic symptoms (26%) were the most common initial signs, offering a systematic breakdown of symptom prevalence that had not been clearly documented before.
This study holds substantial clinical significance, as it enables precise prediction of disease progression and treatment planning based on the mutation type in pediatric patients affected by PAX2 gene mutations.
“Our findings suggest that identifying high-risk patients with truncating mutations can lead to earlier diagnosis and targeted intervention, potentially improving both renal and ophthalmologic outcomes,” said Professor Jihyun Kim. “Delaying disease progression in these patients could greatly enhance their quality of life.”
Professor Kim also emphasized the importance of early screening, stating, “If a child exhibits proteinuria on a urine test or signs like nystagmus, it’s crucial to visit a hospital for a comprehensive examination.”
