A new gene was identified in cooperation with Hacettepe and Munich Technical University

Launched on April 14, 2021, within the scope of the project titled "Investigation of New Genes in Inherited Rare Kidney Diseases", which is a Priority Area Project supported by the Istanbul University-Cerrahpaşa Scientific Research Projects Coordination Unit  in which Prof. Dr. Fatih Özaltın, a faculty member of the Department of Pediatric Nephrology of our university, is the co-investigator, a new gene causing the disease was identified by a scientific study in which 2 children of the parents, who are first-degree cousins, diagnosed with congenital anomaly of the kidney and urinary tract (CAKUT) were investigated.

CAKUT is the most common cause of chronic kidney disease requiring dialysis or kidney transplantation between 0-14 years of age. Structural abnormalities affecting the kidneys and urinary tract are treated under this heading. Some of these may be isolated, while others may be a component of a syndromic structure involving more than one system. Although more than 180 genes whose mutations are known to cause CAKUT have been identified so far, they explain only 10% of CAKUT cases. This suggests that there are many genes whose mutations cause CAKUT that have not yet been identified.

With the Priority Area Project supported by the Istanbul University-Cerrahpaşa Scientific Research Projects Coordination Unit, a joint study with the Pediatric Nephrology Department of Hacettepe University was initiated in 2021 to identify new genes associated with CAKUT. In this study, CAKUT families with consanguinity between parents and more than one affected individual in the family were subjected to scientific research by Prof. Dr. Fatih Özaltın and his team. In one of these families, FOXD2 gene encoding a transcription factor was found by whole exome sequencing.

After the segregation of the detected variant with the disease within the family was shown, it was concluded to be pathogenic by in slico methods. 3D modeling of the protein also showed that the protein structure is different from the wild type.

In order to find additional families worldwide, GeneMatcher was used to find out that there was a family at the Technical University of Munich with another mutation in the same gene and a phenotype similar to ours. We contacted the researchers at the Technical University of Munich and initiated a collaboration. Through in vivo and in vitro studies, the results of the structural defect in the FOXD2 protein were demonstrated and the role of this gene in kidney development was elucidated. While these studies were continuing, after publishing the pre-print form of the study, we were contacted from Israel and informed that they had a similar family and that they had detected another variant in the same gene and that they wanted cooperation, and the third family was identified and the role of the FOXD2 gene in this form of CAKUT was strengthened. Thus, a new gene whose mutations cause CAKUT has been identified and the critical role of FOXD2 in kidney development has been proven by scientific methods.

This study was recently accepted for publication in the Kidney International (Impact factor 19), one of the most prestigious journals in nephrology, with co-contributions from Hacettepe University and Technical University of Munich (first authorship and corresponding authorship shared equally) and published online in December 2023