Abstract: TH-PO0637
Comparative Whole-Exome Sequencing in Patients with Loin Pain Hematuria Syndrome and Isolated Hematuria
Session Information
- Genetic Diseases of the Kidneys: Complex Kidney Traits
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Complex Kidney Traits
Authors
- Prasad, Bhanu, Regina General Hospital, Regina, Saskatchewan, Canada
- Soliman, Ahmed M., University of Regina, Regina, Saskatchewan, Canada
- Garg, Aarti, University of Regina, Regina, Saskatchewan, Canada
- Lanktree, Matthew, McMaster University, Hamilton, Ontario, Canada
Background
Loin pain hematuria syndrome (LPHS) is an ultrarare disease characterized by unexplained chronic loin pain and hematuria, with no identifiable urological causes.
Objectives: To investigate the genetic factors contributing to hematuria and pain in patients with LPHS and isolated hematuria (IH) using whole exome sequencing (WES).
Methods
In this single-center study, 17 consecutive patients with LPHS and 10 with IH underwent WES from Jan 2022-Jan2023. Bioinformatically created hematuria (n=130) and pain (n=577) gene panels were evaluated. Variant annotation, interpretation, and prioritization were performed using the Franklin platform.
Results
A total of 44 variants were identified in 35 hematuria genes.17 and 27 variants were found in 8 IH patients and 16 LPHS patients. In 3 LPHS patients, we detected 3 pathogenic/likely pathogenic (P/LP) missense variants in COL4A4 (c.G3044A:p.Gly1015Glu), ABCA1 (c.2861C>T: p.Ser954Leu) exacerbating glomerular endothelial cell injury by promoting cholesterol accumulation and CXCR4 (c.373C>G: p.Leu125Val) inducing podocyte injury. In another 2 IH patients, we found a missense variant in COL4A5 (c.T4561A:p.Cys1521Ser) and a frameshift deletion in COL4A3 (c.4329_4330del:p.Gly1445Lfs*64). A total of 34 variants of uncertain significance (VUS), including genes affecting podocytes (FAT1, ITGB3, ITGB4, COQ2, APOA1, and GAPVD1), GBM (GPC5, COL4A5), and endothelial cells (CFH, PLG) were also identified. A total of 18 rare variants were found in 17 pain genes unique to LPHS. None of these pain variants were P/LP.
Conclusion
The etiology of hematuria in LPHS displays both genic and allelic heterogeneity. As expected, variants in Type IV Collagen genes (COL4A3-5) were pathogenic, caused hematuria, and were identified in IH and LPHS patients. Many VUS were identified in patients with isolated hematuria and LPHS. To our knowledge, this is the first WES report on LPHS patients globally.
Pathogenic or likely pathogenic variants in hematuria genes identified in this study