A novel <i>Presenilin 2</i> mutation in two siblings with predominantly amnestic, early‐onset Alzheimer’s disease
Bibliographic record
Abstract
Abstract Background Familial, early‐onset Alzheimer’s Disease (AD) is a rare form of dementia resulting from autosomal dominant mutations in the amyloid precursor protein (APP), presenilin‐1 (PSEN1), or presenilin‐2 (PSEN2) genes with phenotypic diversity. PSEN2 mutations are rare and vary widely in age of onset. Method Case report and literature review. Result We report a novel PSEN2 variant (c.359T>G, p.Ile120Ser) that has been clearly segregated in two siblings in their fifties, presenting as predominantly amnestic AD. One of the siblings was also heterozygous in the PSEN1 gene (c.118_120del, p.Asp40del). There was no evidence of C9orf72 repeat expansion in either sibling. A third sibling has also started manifesting cognitive impairments. Their strong family history of cognitive dysfunction suggests that the PSEN2 mutation is pathogenic, and the causative variant has never been reported in Medline and the Alzgene genetic database of PSEN2. Conclusion As there are numerous PSEN2 mutations still incompletely characterized, there remains a need to systematically report patients either with familial or sporadic presentation and very early age of onset and classify their pathogenicity accordingly. Providing information about the genetic bases of AD can help allay the stress of patients and families about their diagnosis, individual risks, and possible care planning.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".