Abstract: SA-PO406
Implementing Comprehensive Genetic Testing in Patients with Kidney Disease Improves Care by Identifying the Basis for a Wide Variety of Renal Phenotypes
Session Information
- Genetic Diseases of the Kidney - III
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1002 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Thomas, Christie P., University of Iowa, Iowa City, Iowa, United States
- Mansilla, M. Adela, University of Iowa, Iowa City, Iowa, United States
- Freese, Margaret E., University of Iowa Hospitals & Clinics, Iowa City, Iowa, United States
- Kimble, Mycah J., University of Iowa, Iowa City, Iowa, United States
- Campbell, Colleen Ann, University of Iowa, Iowa City, Iowa, United States
- Smith, Richard J., University of Iowa, Iowa City, Iowa, United States
Background
The clinical diagnosis of genetic renal diseases may be limited by the overlapping spectrum of manifestations between diseases or by the advancement of disease where clues to the original process is absent. The objective of this study was to determine whether genetic testing informs diagnosis and facilitates management of kidney disease patients.
Methods
We developed a comprehensive genetic testing panel (KidneySeq) to evaluate patients with various phenotypes including cystic diseases, congenital anomalies of the kidney and urinary tract (CAKUT), tubulointerstitial diseases, transport disorders and glomerular diseases. We evaluated this panel in 127 consecutive patients ranging in age from newborns to 81 years who had samples sent in for genetic testing.
Results
The performance of the sequencing pipeline for single nucleotide variants was validated using CEPH controls and for indels using Genome-in-a-Bottle. To test the reliability of the copy number variant analysis, positive samples were re-sequenced and analyzed. For patient samples, a multidisciplinary review board interpreted genetic results in the context of clinical data. A genetic diagnosis was made in 56 (44%) patients and ranged from 56% for ciliopathies/tubulointerstitial diseases, 46% for CAKUT, 45% for transport disorders and 35% for glomerulopathies. Pathogenic and likely pathogenic variants included 46% missense, 13% nonsense, 5% splice site variants, 22% insertion-deletions and 13% copy number variants. In 15 cases, the genetic result changed the clinical diagnosis.
Conclusion
Comprehensive genetic testing should be considered in the evaluation of renal patients as it complements other tests and provides insight into the underlying disease and its management.
Outcome of comprehensive gene panel testing in 127 renal patients