Abstract: FR-PO678
Exome Sequencing in Patients with Loin Pain Hematuria Syndrome
Session Information
- Genetic Kidney Diseases: Cohort Studies - Genetic Associations and Diagnoses
October 25, 2024 | 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: Non-Cystic
Authors
- Prasad, Bhanu, Regina General Hospital, Regina, Saskatchewan, Canada
- Sharma, Aditi, University of Regina, Regina, Saskatchewan, Canada
- Garg, Aarti, University of Regina, Regina, Saskatchewan, Canada
- Schott, Clara, Western University Schulich School of Medicine & Dentistry, London, Ontario, Canada
- Connaughton, Dervla M., Western University Schulich School of Medicine & Dentistry, London, Ontario, Canada
- Lanktree, Matthew Bruce, McMaster University Faculty of Health Sciences, Hamilton, Ontario, Canada
Background
Loin pain hematuria syndrome (LPHS) is a rare clinical syndrome with a reported prevalence of ~1 in 10,000 characterized by severe pain localized to the kidney, and gross or microscopic hematuria. Because of an inadequate understanding of the pathophysiology of the disease, the goal of management has been limited to symptomatic pain management. We used whole exome sequencing to investigate the genetic factors affecting the glomerular filtration barrier, contributing to hematuria in patients with LPHS. We describe herein their phenotypes and variant spectra.
Methods
In this single-center study, 17 consecutive patients with LPHS underwent whole exome sequencing (WES) from Jan 2022 to Jan 2023. A bioinformatically created hematuria gene panel (n = 143) was evaluated. American College of Medical Genetics and Genomics (ACMG) guidelines were followed for interpreting the identified variants.
Results
Among the 17 patients, 13 exhibited overt hematuria, while 4 had microscopic hematuria. 9/17 (53%) patients had a preceding history of kidney stones, but none had an obstructing stone on imaging at the time. Analysis of pedigree charts revealed that 8/17 (43%) patients had a family history of kidney stones, and 3/17 (18%) had a family history of hematuria. None of the 17 patients had a family history of LPHS. A total of 35 variants were identified in 25 of 143 hematuria gene panel genes in 14 patients. 29 of the 35 were variants of uncertain significance. We detected 3 pathogenic or likely pathogenic mutations, including two heterozygous missense variants and a frameshift deletion in COL4A3/4 genes.
Conclusion
In 17 patients with LPHS, 35 variants of uncertain significance were identified among 25 genes reported to impact the glomerular basement membrane and cause hematuria. Determining the causality of these variants is challenging.