Aylin GENÇLER, Özlem ÖZ, Mehmet Burak MUTLU
Turkish Journal of Nephrology - 2026;35(4):312-318
Background: Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of chronic kidney disease in childhood and are frequently associated with monogenic disorders. Whole exome sequencing (WES) has become an important diagnostic tool, particularly in patients with syndromic features or severe kidney phenotypes. This study aimed to investigate the genetic etiology of pediatric CAKUT using WES and to evaluate genotype-phenotype correlations in a carefully phenotyped cohort. Methods: Thirty-one pediatric patients diagnosed with CAKUT were enrolled. Detailed clinical phenotyping was performed, including evaluation of extrarenal manifestations and family history. Whole exome sequencing was conducted, and variants were interpreted according to American College of Medical Genetics and Genomics criteria. Segregation analyses were performed when possible. Results: The overall diagnostic yield of WES was 16.1% (5/31). Pathogenic or likely pathogenic variants were identified in PAX2 , MYCN, KMT2A, CEP290, and a variant of uncertain significance in CHD7. All genetically solved patients presented with bilateral kidney anomalies and/or prominent extrarenal findings suggestive of syndromic disease. The findings were consistent with papillorenal syndrome, Feingold syndrome, Joubert syndrome, and Wiedemann-Steiner syndrome phenotypes. The identification of KMT2A and CEP290 variants in patients with classical CAKUT features suggests that epigenetic regulatory and ciliary genes may contribute to the CAKUT spectrum. Conclusion: Whole exome sequencing provides meaningful diagnostic information in selected CAKUT patients, particularly those with syndromic features. Careful clinical phenotyping is essential to guide genetic testing. The findings expand the understanding of genotype-phenotype relationships in CAKUT and highlight the potential role of emerging genes such as KMT2A and CEP290 in kidney developmental disorders.
