A research team at the Seoul National University Bundang Hospital (SNUBH) has shown for the first time globally that the progression and prognosis of kidney failure and eye abnormalities in patients with the ultra-rare PAX2 gene mutation differ vary depending on the type of mutation, , the hospital announced Thursday.
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A SNUBH research team identified genetic factors influencing the severity of rare PAX2-related kidney and eye disease. From left: Professors Kim Ji-hyun (SNUBH), Ahn Yo-han and Jung Jae-ho (Seoul National University Children’s Hospital). (Credit: SNUBH)
Although kidneys and eyes are typically considered distinct organs, both develop under the influence of the PAX2 gene during fetal growth.
PAX2 mutations 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 kidney 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 (Pediatrics, SNUBH), Ahn Yo-han (Pediatrics), and Jung Jae-ho (Ophthalmology), both from 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 researchers were the first to demonstrate that patients with “truncating” mutations -- those that completely disrupt the structure of the encoded protein -- progressed to end-stage kidney disease much more rapidly than those with “non-truncating” mutations, which preserve partial protein function.
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 mutationswere also more frequently linked to papillorenal syndrome, a condition where both kidney and optic nerve abnormalities are present.
Proteinuria (37%) and ocular symptoms (26%) emerged the most common clinical features in patients with PAX2 mutation, providing a clearer picture of symptom prevalence.
“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.
Source: https://www.koreabiomed.com/news/articleView.html?idxno=27486
