Exome Sequencing in Patients with Loin Pain Hematuria Syndrome
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".