P.131 De novo PIK3CB mutation associated with macrocephaly and diffuse polymicrogyria
Bibliographic record
Abstract
Background: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta (PIK3CB) is a member of the PI3K complex. This complex has two p110 members; PIK3CA (p110a) and PIK3CB (p110b) which are both ubiquitously expressed. PI3K complex functions to phosphorylate PIP2 to PIP3 which activates AKT and subsequently mTOR. PIK3CA mutations have been previously linked with macrocephaly and developmental delay. Methods: An 18 month old girl was investigated for severe hypotonia, developmental delay and macrocephaly. Head circumference was >97%ile at birth and 53.0 cm (>99%ile, +5.4 SD) at 13 months old. She had no hydrocephalus or epilepsy. MRI brain (18 months old) re-identified megalencephaly and diffuse polymicrogyria. Symmetric signal abnormality was noted in the periventricular white matter, unchanged between 8 and 18 month images. MR spectroscopy was unrevealing. At 18 months she remains unable to sit independently. Exome sequencing was performed and functional studies to further support variant pathogenicity. Results: Exome sequencing identified de novo variant in PIK3CB: c.1735G>T; p.Asp579Tyr. No mutations were noted in other genes known to cause developmental delay, macrocephaly or overgrowth syndromes. Functional studies in patient cells showed dysregulation of PIK3CB and downstream signalling, providing support for causality of this novel disease gene. Conclusions: We believe that our patient’s macrocephaly (+5.4 SD) and diffuse polymicrogyria results from altered PIK3CB 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) | 0.003 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.003 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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".