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Abstract: SA-PO769

Molecular Testing in a Clinical Laboratory Cohort Reveals Significantly Increased Incidence of PKD1 Truncating Variants in ADPKD Patients with Pediatric-Onset vs. Adult Presentation

Session Information

Category: Genetic Diseases of the Kidneys

  • 1201 Genetic Diseases of the Kidneys: Cystic


  • Sulmonte, Laura AG, GeneDx, LLC, Stamford, Connecticut, United States
  • Ustach, Vincent D., GeneDx, LLC, Stamford, Connecticut, United States
  • Celestino Soper, Patricia, GeneDx, LLC, Stamford, Connecticut, United States

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a multisystem disorder characterized by multiple kidney cysts and extrarenal features. PKD1 and PKD2 (likely) pathogenic (L/PATH) variants cause 95% of ADPKD. Although the majority of ADPKD cases present in adulthood, approximately 1-2% have onset before age 15. While severe presentation is usually associated with truncating PKD1 variants in adults, the variant spectrum in pediatric ADPKD cases is not well-established.


We examined the age distribution and variant spectrum in pediatric and adult cases in a retrospective study of 1582 cases referred for next generation sequencing multi-gene panel clinical testing for Cystic Kidney Disease (CKD). Testing included sequence and copy number analysis of PKD1, PKD2, PKHD1 and other genes associated with renal cysts.


The pediatric sub-cohort accounted for nearly one-third of cases tested. Our analysis revealed a diagnostic rate of 42% for the entire cohort and involved 13 genes (40% within adult and 46% within pediatric sub-cohorts – including ADPKD patients with prenatal onset). Diagnostic cases primarily had L/PATH variants in PKD1 (69%) or PKD2 (16%), but also included HNF1B (2% adult, 16% pediatric), bi-allelic PKHD1 (1% adult, 7% pediatric) and GANAB (2% adult, 2% pediatric). Truncating PKD1 L/PATH variants were significantly enriched in both our pediatric (p-value<0.001) and adult (p-value<0.001) sub-cohorts. A statistically significant association was found between the age groups and variant types (p-value<0.05), with 68.9% of L/PATH variants in pediatric patients being PKD1 truncating compared to 59.8% in adults.


Consistent with published data, our results indicated that PKD1 L/PATH variants, particularly truncating, were the cause of the majority of ADPKD, regardless of age of onset or presentation. Additionally, we found that PKD1 truncating variants were more significantly enriched in the pediatric cohort compared to adults. Lastly, findings from clinical genetic testing for patients with CKD may inform clinical management, guide decision-making for reproductive and familial cascade testing, and generate research questions to better characterize genotype-phenotype correlations that may impact future patient care.