Biallelic <i>SIDT2</i> loss-of-function in a child with cerebellar ataxia and lysosomal dysfunction mimics impairment of <i>SIDT2</i> in mice
Bibliographic record
Abstract
SIDT2 (Systemic Interference Deficient 1 Transmembrane Family Member 2) is a lysosomal membrane protein involved in RNA degradation via RNAutophagy. While animal models have indicated a link between SIDT2 deficiency and lysosomal storage disorders, no human cases have been reported. Here, we report a child with biallelic SIDT2 missense variants (p.Arg529Trp, p.Arg678Trp), who developed progressive neurological decline with cerebellar atrophy and Parkinsonian features. Functional studies revealed that the affected individual’s variants disrupted the ability of SIDT2 to interact with RNA. Fibroblasts from the affected individual showed impaired autophagy, characterised by abnormal accumulation of autophagy markers. In mouse models, Sidt2 was found to be highly expressed in the brain, particularly in the hippocampus and cerebellum. Sidt2 loss-of-function in mice resulted in not only impaired autophagy in the brain but also neurological dysfunction, including motor incoordination and eventual seizures. These findings suggest that SIDT2 deficiency contributes to both autophagic dysfunction and neurodegenerative processes, providing insight into a potential role in human neurological disease.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.002 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".