Abstract: SA-PO574
Exome Sequencing "Firsthand" for Polycystic Kidney Diseases: Impact beyond PKD1/PKD2 Identification on ADPKD Clinical Management
Session Information
- Cystic Kidney Diseases: Genetic Causes, Modifiers, and Extrarenal Manifestations
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Cystic
Authors
- Mesnard, Laurent, Sorbonne Universite, Paris, Île-de-France, France
- Bensouna, Ilias, Sorbonne Universite, Paris, Île-de-France, France
- Serveaux Dancer, Marine, Eurofins Biomnis Lyon, Lyon, France
- Robert, Thomas, Assistance Publique Hopitaux de Marseille, Marseille, France
- Doreille, Alice, Montreal General Hospital, Montreal, Quebec, Canada
Background
Genetic testing is currently considered non-mandatory for managing typical autosomal dominant polycystic kidney disease (ADPKD) patients. However, an increasing number of genes are associated with ADPKD. For atypical forms of ADPKD, the diagnostic yield may be lower with targeted genetic analysis. Genome-wide analysis can highlight incidental findings that could impact clinical management. Recent studies suggest that exome sequencing (ES) could be as efficient as standard methods, even for PKD1/PKD2 analysis.
Methods
Among 3523 index cases undergoing ES genetic testing at Sorbonne University, Paris, France, 721 patients were categorized as having cystic diseases (149 with typical ADPKD and 572 with atypical ADPKD). We compared the diagnostic yield in both typical and atypical ADPKD. Then, we analyzed the rate of incidental findings impacting ADPKD clinical management (pathogenic variants not anticipated that explain part of the phenotype, or for which the patient is not/pre-symptomatic, or variants of interest in genetic counseling) among patients with a pathogenic variant in PKD1/PKD2 genes and compared this to the entire cystic nephropathy cohort.
Results
Of the 721 patients with cystic nephropathy, 239 had a positive genetic test with a pathogenic or likely pathogenic variant (33%). The diagnosis rate was 59.1% for typical ADPKD patients compared to 26.4% in the atypical cystic nephropathy population. In the typical ADPKD group, PKD1 and PKD2 represented only 60.3% of pathogenic variants found by ES. Double hits represented 13.1% of patients with a positive genetic test, reaching 20.6% in the PKD1/PKD2 population.
Conclusion
Our results showed a great diversity in genes responsible for adult’s cystic nephropathies, even in the typical ADPKD population. We observed a significant rate of incidental findings impacting clinical ADPKD management. Our work suggests that ES should be considered a first-tier test for any ADPKD patients to optimize their clinical management.
Percentage of patients carrying a second variant in a second gene among patients with a positive genetic diagnosis.