Exome Sequencing in Saudi Arabian Pediatric Kidney Disease Single-Center Cohort

In pediatric patients, monogenic causes are a significant contributor to kidney disease, ranging from approximately 10% in congenital anomalies of the kidney and urinary tract (CAKUT) to about 55% in renal ciliopathies. Exome sequencing has revealed numerous disease-causing genes and pathogenic variants. Nevertheless, continuous efforts are crucial to expand the knowledge base of these variants to establish unequivocal diagnoses. In this study, we report exome sequencing data from a single Saudi Arabian center, aiming to explore potential founder effects and determine specific genotype-phenotype correlations based on clinical diagnoses and genetic ancestry.

We consolidated 487 families with glomerular disease, CAKUT, cystic kidney disease, stone disease, and tubulopathies, recruited between 2007 and 2023 at King Abdulaziz University in Jeddah, Saudi Arabia. In these families, we performed exome sequencing and analyzed the data obtained for variants in established disease genes.

In this highly consanguineous cohort (54%), 195 of 487 participants (40%) had glomerular disease, 160 of 487 (33%) had CAKUT, 44 of 487 (9%) had cystic kidney disease, 40 of 487 (8%) had stone disease, and 34 of 487 (7%) had tubulopathies. Pathogenic variants were identified in 45% of families with glomerular disease, 21% with CAKUT, 77% with cystic kidney disease, 58% with stone disease, and 76% of families with tubulopathy.

We identified a likely genetic cause of kidney disease in 43% of participants. Elucidating prevalent disease genes and disease variants in a defined region and genetic ancestry group provides important insights into variant pathogenicity assessment, disease management, and prognosis.