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Abstract: TH-PO658

Whole Exome Sequencing Identifies Several Patients with Undiagnosed Autosomal Dominant Polycystic Kidney Disease in an Unselected Cohort

Session Information

Category: Genetic Diseases of the Kidney

  • 1001 Genetic Diseases of the Kidney: Cystic


  • Abdalla, Yoosif, Geisinger, Danville, Pennsylvania, United States
  • Luo, Jonathan Z., Geisinger, Danville, Pennsylvania, United States
  • Green, Jamie Alton, Geisinger, Danville, Pennsylvania, United States
  • Mohan, Prince, Geisinger Medical Center, Danville, Pennsylvania, United States
  • Mirshahi, Tooraj, Geisinger, Danville, Pennsylvania, United States
  • Chang, Alex R., Geisinger, Danville, Pennsylvania, United States

The utility of whole exome sequencing (WES) to identify genetic causes of end-stage renal disease (ESRD) such as autosomal dominant polycystic kidney disease (ADPKD) is uncertain.


We used WES data from the Geisinger-Regeneron DiscovEHR cohort, an ongoing health system-based genetics study, to identify patients with putative loss of function (pLOF) PKD1 and PKD2 mutations. Clinical evidence of ADPKD was ascertained using electronic health record data [diagnosis codes, estimated glomerular filtration rate (eGFR), family history], and confirmed by chart review. We considered ADPKD to be undiagnosed if there was no mention of the diagnosis in clinic notes.


Out of 91,365 adults with WES data, we identified 87 (66 PKD1, 21 PKD2) patients with pLOF mutations. A total of 44 (29 PKD1, 15 PKD2) patients had previously been diagnosed with ADPKD, including 24 (21 PKD1, 3 PKD2) patients with ESRD ((Figure). Of the remaining 43 patients without existing ADPKD clinical diagnoses, 24 had imaging data available, and 5 had radiologic findings suggesting ADPKD (3 with multiple renal and liver cysts, 2 with multiple bilateral renal cysts). One of the 5 patients with undiagnosed ADPKD had PKD2 pLOF mutation, ESRD at the age of 70 attributed to hypertension and diabetes and a brother with ESRD attributed to diabetes. The remaining 4 patients with radiologic findings suggesting ADPKD but no clinical diagnosis had eGFR ranging from 48 to 129 ml/min/1.73m2). There were 19 patients with renal imaging (18 PKD1, 1 PKD2) who had no renal cysts.


Population-based WES may provide an opportunity to identify previously undiagnosed ADPKD patients who could benefit from targeted treatment and family counseling. Additional targeted sequencing will be needed to confirm WES results for PKD1 mutations.


  • NIDDK Support