Abstract: SA-PO802
Diagnostic Utility of Whole Exome Sequencing in Adults with CKD and Biological Markers of Thrombotic Microangiopathy
Session Information
- Genetic Diseases: Glomerulopathies - II
November 04, 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
- Lombardi, Yannis, Assistance Publique - Hopitaux de Paris, Paris, Île-de-France, France
- Rafat, Cedric, Assistance Publique - Hopitaux de Paris, Paris, Île-de-France, France
- Doreille, Alice, Assistance Publique - Hopitaux de Paris, Paris, Île-de-France, France
- Garcia, Hugo, Assistance Publique - Hopitaux de Paris, Paris, Île-de-France, France
- Mousseaux, Cyril, Assistance Publique - Hopitaux de Paris, Paris, Île-de-France, France
- Luque, Yosu, Assistance Publique - Hopitaux de Paris, Paris, Île-de-France, France
- Mesnard, Laurent, Assistance Publique - Hopitaux de Paris, Paris, France
Background
Chronic kidney disease (CKD) in adults may be associated with biological markers of thrombotic microangiopathy (TMA), defined as a mechanical hemolytic anemia with a decreased platelet count. In a number of cases, even after an extensive investigation including the search for variants in genes regulating the complement pathway, a definitive diagnosis cannot not be achieved. Whole Exome Sequencing (WES), which examines the entire coding regions of the genome, could be of interest in these clinical forms.
Methods
We included all consecutive adult patients who underwent WES for CKD of unknown origin between 10/10/17 and 31/12/22 in the Nephrology Department of Sorbonne University (Tenon and Pitié-Salpêtrière hospitals). The collection of clinical characteristics, including the presence of biological markers of TMA, is prospectively done by the prescribing physician. We retrospectively assessed whether patients had been accurately classified (Figure 1). All diagnoses were made according to the guidelines of the American College of Medical Genetics and Genomics.
Results
During the study period, 1410 patients underwent WES, and 193/1410 (14%) exhibited biological markers of TMA. Among them, WES identified a variant consistent with the renal phenotype in 31/193 (16%) cases. 22/31 (71%) did not involve genes regulating the alternative complement pathway: type 4 collagens (COL4A3, COL4A4, COL4A5) (n=7); nephronophthisis-associated genes (TTC21B, NPHP3, NPHP4) (n=5); IFT140 (n=2); TRPC6, PAX2, SOX18, HNF1A, MMACHC, SPTB, and MT-TL1 (n=1 each). Complement-related disorders involved CFH (n=4), CFI (n=3), CD46 and C2 (n=1 each).
Conclusion
Whole Exome Sequencing of 193 patients with CKD associated with TMA resulted in a diagnosis in 31/193 (16%) of the cases, and 22/31 (71%) diagnoses did not involve the alternative complement pathway.