Alu-element insertion in the homeodomain of<i>HESX1</i>and aplasia of the anterior pituitary
Bibliographic record
Abstract
The pathophysiology of combined pituitary hormone deficiency is just beginning to be elucidated. None of the genes known to be necessary for pituitary development has so far been involved in pituitary gland aplasia in humans. Among these, Hesx1/HESX1, which encodes a homeobox transcription factor, has been shown to be essential for normal forebrain development in mice, and HESX1 mutations in humans have been associated with various pituitary hormone deficiencies usually combined with optic nerve anomalies. Here we have investigated a consanguineous family in which two siblings displayed a complete absence of the anterior pituitary revealed by a deficit in all anterior pituitary hormones. One patient, who also has retinal coloboma, carries a HESX1 defect in the homozygous state: an Alu insertion in exon 3, a sequence that encodes the major part of the homeodomain. The Alu-containing HESX1 allele generates a major transcript lacking this exon, and a minor one in which exons 2 and 3 are skipped, predicting severely truncated proteins. This observation, which combines pituitary aplasia and retinal coloboma, further illustrates the heterogeneity of HESX1-associated disease phenotypes. Anterior pituitary aplasia is a new example of a human disease caused by a germline retrotransposition event involving an Alu sequence.
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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".