P.074 Clinical features of a family with distal myopathy and rimmed vacuoles due to a digenic interaction
Bibliographic record
Abstract
Background: The interaction between mutations in two or more genes is increasingly recognised as an important contributor to the phenotypic variability in genetic disorders. Co-occurrence of variants in SQSTM1 and TIA1 is reported as a cause of myopathy in 3 prior cases, but limited clinical data were presented. We present detailed clinical features of a family with two siblings having a distal myopathy with rimmed vacuoles (DMRV), and genetic variants in SQSTM1 and TIA1. Methods: Clinicopathologic study of a family with DMRV to describe clinical features, laboratory and neurophysiology studies, neuroimaging, and genetic sequencing. Results: Two siblings with variants in SQSTM1 and TIA1 developed myopathy in their early 60’s, with early involvement of ankle dorsiflexors and finger extensors. A decade after onset, patients remain ambulatory and have not developed cardiac or respiratory complications. MRI of the legs showed selective involvement of adductor magnus, vastus lateralis, and in lower legs the anterior compartment and medial gastrocnemius. Muscle pathology demonstrated rimmed vacuoles, disrupted myofibrillar architecture, and mislocalised TDP43. Two unaffected family members had one genetic variant but not both. Conclusions: We describe a fourth family with co-occurrence of TIA1 and SQSTM1 genetic variants and describe their detailed phenotype. Future study should address the mechanism of the interaction between these two variants.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.009 | 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".