Abstract: FR-PO627
Utility of a Renal Genetics Clinic: A Canadian Prospective Cohort
Session Information
- Genetic Diseases: Tubulopathies
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Schott, Clara, Western University Schulich School of Medicine & Dentistry, London, Ontario, Canada
- Baker, Cadence, London Health Sciences Centre, London, Ontario, Canada
- Colaiacovo, Samantha, London Health Sciences Centre, London, Ontario, Canada
- Connaughton, Dervla M., London Health Sciences Centre, London, Ontario, Canada
Background
Genetic kidney disease (GKD) is more prevalent than previously considered, with 1 in 10 chronic kidney disease (CKD) patients affected. When correct inclusion criteria for GKD is used, 34-67% of patients can have a genetic diagnosis. Genomic testing using gene-panel or exome sequencing (ES) can confirm GKD through detection of mutations in genes known to cause CKD. Unfortunately, widespread integration into clinical practice has been hampered by small studies and highly selective populations predominately performed in research rather than clinical settings. This study aims to prospectively demonstrate the utility of a renal genetics clinic in a Canadian cohort.
Methods
We analyzed data from a cohort of patients (n=174 families, n=209 affected patients) referred to a renal genetic clinic between September 2019 and April 2023. Testing strategy was firstly to perform gene-panel testing, and if negative or unsuitable, ES was performed. Testing was performed for the detection of mutations in genes suspected to cause the specific subtype of CKD. Mutations are classified according to the American College of Medical Genetics guidelines, with pathogenic and likely pathogenic variants being causative.
Results
We identified a causative mutation in a gene known to cause CKD in 38% of patients (n=80/209). Gene panel testing, performed as the first line of investigation, detected the underlying molecular cause of CKD in 31% of patients tested (n=44/142). Primary ES was performed as the first test in patients with CKD of unknown etiology (CKDu) and had a solve rate of 18% (n=8/45). In patients whom gene-panel was negative or not possible (n=82), secondary ES analysis was performed and confirmed the suspected clinical diagnosis in 26% of patients (n=21/82). For solved patients (n=80), there were many clincial outcomes, including change of diagnosis. Of note, 48% of solved patients had a pre-priori diagnosis of CKDu, but all receied a diagnosis after testing. Other important clinical outcomes include, avail of genetic counselling, resolved diagnostic confusion, and correction of diagnosis.
Conclusion
We show that in a Canadian cohort of adults referred to a renal genetic clinic, genomic testing has utility by confirming the cause of genetic kidney disease in 38% of patients. Genetic sequencing also has significant impacts on clinical management and patient outcomes.