P.134 Infantile Onset Multisystem Neurologic, Endocrine and Pancreatic Disease: case series and review
Bibliographic record
Abstract
Background: We report three brothers born to consanguineous parents of Syrian descent with a novel homozygous c.324G>A (p.W108*) mutation in PTRH2 that encodes mitochondrial peptidyl-tRNA hydrolase 2. Mutations in PTRH2 have recently been identified in the autosomal recessive condition, Infantile Onset Multisystem Neurologic, Endocrine and Pancreatic Disease (IMNEPD). To our knowledge, this is the first case of IMNEPD described in a Canadian centre. Methods: Clinical phenotyping enabled a targeted approach in which all exons of PTRH2 were sequenced. We identified a novel mutation and compared our patients with those recently described. Results: We identified a homozygous nonsense mutation in PTRH2, c.324G>A (p.W108*). This G to A mutation results in a premature stop at codon 108 that produces a truncated protein, removing most of the amino acids at the enzymatic active site. This mutation is not listed in the human Gene Mutation Database Cardiff, NCBI dbSNP, 1000 Genomes, Exome Variant Server or ClinVar and is a rare variant listed in gnomAD. Conclusions: In IMNEPD, nonsense mutations in PTRH2 appear to cause severe disease with postnatal microcephaly, neurodevelopmental regression, and ataxia with additional features of seizures, peripheral neuropathy, and pancreatic dysfunction, whereas missense mutations may produce a milder phenotype. The spectrum exhibited by our patients suggests variable expressivity with PTRH2 mutations.
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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) | 0.001 | 0.001 |
| Bibliometrics | 0.007 | 0.006 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.003 |
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".