Abstract: SA-PO405
Diagnostic and Clinical Utility of Whole-Exome Sequencing in a Cohort with Clinically Suspected Genetic Kidney Disease
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
- Jayasinghe, Kushani C., Monash Health, Clayton, New South Wales, Australia
- Mallett, Andrew John, Royal Brisbane and Women's Hospital, Stafford, Queensland, Australia
- Quinlan, Catherine, The Royal Children's Hospital, Melbourne, Victoria, Australia
Group or Team Name
- Melbourne Genomics Renal Genetics Flagship part of the KidGen collaborative
Background
Genomic technologies enable rapid and cost-effective sequencing of DNA and have demonstrated a definitive diagnosis in several patient groups such as childhood syndromes and oncology. We sought to determine the diagnostic and clinical utility of WES in a cohort of adults and children with clinically suspected genetic kidney disease who were reviewed in multidisciplinary renal genetics clinic (RGC).
Methods
Sequential patients were prospectively recruited through five tertiary academic centres in Australia. Patients were referred by their treating nephrologist to a dedicated RGC. Following review by a multidisciplinary team consisting of a nephrologist, clinical geneticist and genetic counsellor, patients underwent genomic sequencing with analysis for a pre-determined phenotype specific list of genes of interest. We measured the diagnostic yield and the effect on short term clinical management. Full author list online at KidGen.org.au
Results
We performed WES in 204 patients (82 paediatric and 122 adults) with CKD. The median age at time of recruitment was 29 years (0-72). Preliminary results demonstrate a genetic diagnosis in 77 patients (38%). This includes (69) pathogenic variants and (25) likely pathogenic variants. When comparing the a priori clinical diagnosis at referral in patients with WES diagnoses, 48 (62%) had their suspected clinical diagnosis confirmed and 29 patients (38%) had a subsequent change in diagnosis. 42 patients (54%) with positive diagnoses had recommended changes to clinical management. This included the avoidance of immunosuppression, avoidance of renal biopsy, initiation of surveillance for extra-renal disease and facilitating transplant and reproductive decisions. In addition, at least 26 patients (13%) had a clinically relevant negative result with management implications.
Conclusion
To our knowledge this is the first study to report diagnostic and clinical utility of genomic sequencing in a pragmatic clinical setting. Our results confirm that in a clinically selected paediatric and adult cohort with kidney disease, WES is valuable for establishing a specific molecular diagnosis and demonstrates substantial quantifiable clinical utility.
Baseline Characteristics
Funding
- Government Support - Non-U.S.