Identification of a Novel Missense Mutation That Is as Damaging to DAX-1 Repressor Function as a Nonsense Mutation
Bibliographic record
Abstract
Mutations in the DAX-1 (NROB1) gene result in X-linked congenital adrenal hypoplasia (AHC) and hypogonadotropic hypogonadism. The clinical presentation is usually as adrenal insufficiency in early life, with hypogonadotropic hypogonadism detected at the time of expected puberty. In this study we identified mutations in the DAX-1 gene of two patients with AHC. One mutation, Y399X, resulted in a premature stop codon and was associated with loss of Leydig cell responsiveness to human chorionic gonadotropin. The second, L297P, was a missense mutation, and human chorionic gonadotropin responsiveness was maintained. Kindred analysis established that the mutations had been inherited from the proband's mothers. The L297P has not been described previously and occurs within a highly conserved binding motif (LLXLXL). Transient transfection assays demonstrated that both mutations resulted in a severe loss of DAX-1 repressor activity. Immunohistochemical analysis of testicular tissue obtained from an affected sibling of the subject with the Y399X mutation, who had died with adrenal failure as a neonate, showed normal testicular morphology and expression of DAX-1, steroidogenic factor-1, and anti-Mullerian hormone protein. These data extend the clinical and molecular information on DAX-1 mutations, confirm normal testicular development at the neonatal stage, and illustrate variability in Leydig cell function.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 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 | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".