Missense <i>ABI2</i> variants linked to a neurodevelopmental disorder with intellectual disability, epilepsy, hypoplasia of the corpus callosum, and white matter abnormalities
Bibliographic record
Abstract
Abstract The Abelson-interactor 2 gene ( ABI2) encodes a protein that functions as a regulator of Rac-dependent actin cytoskeleton dynamics, a highly coordinated structural framework essential for maintaining intracellular homeostasis and vital in processes such as cell adhesion, communication, membrane transport, migration, cell growth, and development. As a component of the Rac-1 activated WAVE regulatory complex (WRC), ABI2 initiates the actin polymerization machinery Arp2/3 to drive lamellipodia formation, and underlying key cellular processes such as axonal guidance, cell motility, and cell adhesion. Additionally, ABI2 acts as a substrate for non-receptor tyrosine kinases ABL1 and ABL2, with downstream effects controlling neuronal differentiation and migration involved in neocortical development. Here, through exome sequencing and international collaborations, we identify eight unrelated individuals with severe neurodevelopmental delays linked to heterozygous ABI2 missense variants, including a recurrent p.Tyr491Cys in the highly conserved SH3 domain in six individuals. These variants arose de novo in cases where parental testing was available, and were associated with moderate to severe motor delay, absent or delayed expressive language, intellectual disability, seizures, autistic traits, as well as macrocephaly, thinning of the corpus callosum, and remarkable white matter signal abnormalities. This report adds ABI2 to the list of genes implicated in neurodevelopmental disorders, with an additional focus on epilepsy and brain malformations.
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 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) | 0.002 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".