Whole Exome Sequencing in Chinese Pediatric Patients With Nephrolithiasis.

INTRODUCTION

The incidence of pediatric nephrolithiasis has been increasing, and the role of genetic factors has garnered attention in recent years. This study aimed to explore the genetic basis underlying pediatric nephrolithiasis in Chinese population.

METHODS

Whole exome sequencing (WES) was conducted in a consecutive cohort of 456 children over a 11-year period. Clinical and genetic data were systematically collected, analyzed, and comprehensively compared.

RESULTS

Average age was 4.2 years with a male-to-female ratio of 2.2. A total of 260 causative variants in 16 genes were identified in 141 children, resulting in a positive molecular diagnosis rate of 31%. Of the causative variants, 43% were novel. The most prevalent diagnoses were primary hyperoxaluria (PH) (: 20%, : 11%, and : 24%) and cystinuria (: 18% and : 14%). Children with positive molecular diagnoses were more likely to have stone episodes, bilateral stones, multiple stones, or nephrocalcinosis (all < 0.05). Children with defects were more prone to have severe clinical manifestations, and those with defects and males with and defects tended to be diagnosed at a younger age. The concordance rate between suspected clinical diagnoses and molecular diagnoses was 81%. At least 29% of children could benefit from additional clinical advice based on a molecular diagnosis.

CONCLUSION

A genetic etiology was identified in 141 of 456 of pediatric patients (31%) with nephrolithiasis in a Chinese cohort. A positive molecular diagnosis is a risk factor for severe clinical presentation of pediatric nephrolithiasis. WES has the potential to be used to confirm or even modify clinical diagnoses, thereby facilitating individualized therapeutic and preventive interventions.