Diagnostic utility of whole exome sequencing in pediatric and adult patients with suspected monogenic chronic kidney disease.

BACKGROUND

Whole Exome sequencing (WES) is emerging as the primary diagnostic strategy for chronic kidney disease (CKD), a major public health concern, and its diagnostic yield is dependent on the patient selection criteria and techniques used.

METHODS

This study aimed to investigate molecular defects in patients with clinically suspected monogenic CKD using WES. A total of 160 pediatric and adult patients presenting with diverse chronic kidney disorders were enrolled; 134 were subjected to WES analysis.

RESULTS

WES identified genetic causes in 89 patients, with a diagnostic yield of 66.4%. A total of 55 variants were characterized among our CKD patients, including 45 different pathogenic or likely pathogenic variants and ten variants of uncertain significance. The diagnostic yield for the pediatric group was 76.4%, which was greater than that of the adult group (23.6%). Among the 89 patients, the molecular diagnosis aligned with the initial clinical findings in 63 patients (70.7%), refined the clinical diagnosis in five patients (5.6%), and led to a complete reclassification of the original diagnosis in 21 patients (23.6%).

CONCLUSIONS

Our findings demonstrate the robust diagnostic and clinical genetic value of WES in a broad spectrum of kidney diseases.