Mutational Analysis of the Genes Encoding RFAmide‐Related Peptide‐3, the Human Orthologue of Gonadotrophin‐Inhibitory Hormone, and its Receptor (<scp>GPR</scp>147) in Patients with Gonadotrophin‐Releasing Hormone‐Dependent Pubertal Disorders
Bibliographic record
Abstract
RFamide-related peptide-3 (RFRP-3), the orthologue of avian gonadotrophin-inhibitory hormone, and its receptor GPR147 have been recently identified in the human hypothalamus, and their roles in the regulation of reproductive axis has been studied. The present study aimed to investigate whether the presence of variants in the genes encoding human RFRP-3 (NPVF gene) and its receptor, GPR147 (NPFFR1 gene), is associated with the occurrence of gonadotrophin-releasing hormone-dependent pubertal disorders. Seventy-eight patients with idiopathic central precocious puberty (CPP) and 51 with normosmic isolated hypogonadotrophic hypogonadism (nIHH) were investigated. Fifty healthy subjects comprised the control group. The coding sequences of the NPVF and NPFFR1 genes were amplified and sequenced. Odds ratios (OR) were used to estimate the likelihood of CPP or nIHH in the presence of the described polymorphisms. All such polymorphisms have already been registered in the National Center for Biotechnology Information database. A three-nucleotide in frame deletion was identified in the NPVF gene (p.I71_K72), with a smaller proportion in the CPP (5%) compared to the nIHH (15%) group (P = 0.06). This results in the deletion of the isoleucine at position 71, adjacent to lysine at an endoproteolytic cleavage site of the precursor peptide. This polymorphism was associated with a lower risk of CPP (OR = 0.33; 95% confidence interval = 0.08-0.88); interestingly, only two men with nIHH were homozygotes for this variant. A total of five missense polymorphisms were found in the NPFFR1 gene, which encodes GPR147, with similar frequencies among groups and no association with pubertal timing. Our data suggest that RFRP-3/GPR147 may play secondary, modulatory roles on the regulation of pubertal development; a restraining modulatory effect of the NPVF p.I71_K72 variant on the activation of the gonadotrophic axis cannot be ruled out and deserves further investigation.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".