Turkish experts discovered a mutation in a protein-coding gene as a significant factor leading to chronic kidney failure in children, contributing the finding to the international medical literature for the first time.
Dr. Fatih Ozaltin, faculty member of the Department of Pediatric Nephrology of Hacettepe Unversity, told Anadolu that the scientific study for the FOXD2 protein code gene was initiated in 2021 and conducted in collaboration with Istanbul University Cerrahpasa Faculty of Medicine and the Technical University of Munich.
Ozaltin noted that two siblings diagnosed with congenital anomalies of the kidney and urinary tract (CAKUT), leading to chronic kidney failure, were examined at Cerrahpasa Faculty of Medicine.
He said the children were born as a result of consanguineous marriage, prompting an investigation into genetic factors within the family.
Ozaltin said the genetic studies of the research supported within the scope of the project titled, “Investigation of New Genes in Inherited Rare Kidney Diseases,” were carried out at Hacettepe University.
“Our scientific study led us to the FOXD2 gene. We have initiated further research on how mutations in this gene lead to CAKUT anomalies.”
- Gene regulates vital stages in the development of babies' kidneys
Ozaltin highlighted international collaboration, revealing the identification of another family with a mutation of the same gene by Technical University of Munich.
“Through collaboration and our study, they have revealed that the FOXD2 gene plays a crucial role in ‘regulating a vital stage in kidney development in fetuses.' And in the development of the urinary system,” he said. “We have also demonstrated this through various animal experiments. We observed that in animals where the FOXD2 gene is silenced, similar kidney problems to those in humans arise.”
- First time in the world
Ozaltin emphasized the comprehensive study's preliminary results have been published, noting that experts from Israel have reported similar cases in patients.
“We identified three different mutations in the same gene and three different families for a sporadic disease worldwide. This finding became one of the most significant pieces of evidence proving that the disorder in the FOXD2 gene is responsible for CAKUT anomaly.
“The relationship between the mutations in the FOXD2 gene was previously known, but the consequences it caused were unknown, and the CAKUT anomaly was established for the first time in the world in this study,” he said.
-Health issue of congenital origin
“This anomaly stands as the foremost cause of end-stage kidney failures in children, necessitating dialysis and transplantation. It is a significant health issue of congenital origin arising from developmental problems related to the kidneys in the mother's womb,” said Ozaltin.
He emphasized the importance of understanding the genetic aspects of CAKUT.
“The families with the FOXD2 gene mutations that we identified could sustain their lives with relatively preserved kidney functions for a long time, but currently, they are also experiencing kidney failure. In some severe cases, babies require dialysis from the day they are born,” said Ozaltin.
He also underscored the study's significance in elucidating the disease's underlying mechanisms and developing appropriate treatments.
Regarding risk factors, Ozaltin highlighted consanguineous marriages as the most critical risk factor for CAKUT, stating it is not only specific to this disease but applies to all rare diseases.
He added that informing families and avoiding consanguineous marriages are crucial steps in reducing the ratio of rare diseases.
