RET Gly691Ser mutation is associated with primary vesicoureteral reflux in the French-Canadian population from Quebec
Bibliographic record
Abstract
Primary vesicoureteral reflux (pVUR) is a common, genetically heterogeneous congenital urinary tract abnormality in children. It causes urine to flow backward from the bladder to the ureter due to a developmental defect at the vesicoureteral junction, whose formation requires rearrangement during transformation (Ret)-mediated signaling pathways. To study the genetic causes of pVUR in Quebec patients, we used a sequencing-based candidate gene approach to screen the RET gene and found that 83 out of 118 pVUR patients are carriers of the rare A allele of single nucleotide polymorphism (SNP) rs1799939:G>A that results in a Gly691Ser mutation, a statistically significant increase in allelic frequency, that is absent at six flanking RET SNPs tested. Ser691 is a predicted phosphorylation site and our analysis of transfected cells showed that the Gly691Ser Ret mutant can efficiently interact and associate with a 75-80-kD tyrosine phosphorylated cellular protein, an event not seen with wild-type Ret. This interaction and/or the steric or electric hindrance created by phospho-Ser691 may interfere with the known regulatory functions of the normally phosphorylated phospho-Tyr687 and phospho-Ser696 on the cytoskeleton actin reorganization that are responsible for cell motility and morphology, which consequently may lead to the deficiency in ureteral development observed in pVUR. Our study demonstrates that the Ret Gly691Ser mutation is associated with pVUR and may be one of the genetic causes of this condition in the French-Canadian population in Quebec.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| 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".