Mutation in <i>RNF170</i> causes sensory ataxic neuropathy with vestibular areflexia: a CANVAS mimic
Bibliographic record
Abstract
Sensory neuronopathy or ganglionopathy is a type of peripheral neuropathy characterised by primary and selective destruction of the dorsal root ganglia leading to degeneration of both central and peripheral neurites of sensory neurons.1 There is a narrow differential diagnosis for a sensory ganglionopathy which includes paraneoplastic (anti-Hu antibodies), autoimmune (Sjogren syndrome,), toxic (cisplatin, pyridoxine) and genetic (Friedreich’s ataxia and mitochondrial disease due to POLG1 mutations) causes.2 More recently biallelic AAGGG expansion in replication factor complex subunit 1 have been identified as a major cause of sensory ataxia neuropathy, often with cerebellar and vestibular involvement (CANVAS).3 4 However, a significant fraction of patients with a sensory ganglionopathy remain genetically undiagnosed. In 2004 Valdamanis et al identified a heterozygous p.Arg199Cys mutation in ring finger protein 170 ( RNF170 ) responsible for a rare form of sensory ataxia in two families from eastern Canada sharing a founder haplotype.5–7 Affected cases showed progressive sensory loss and ataxia due to degeneration of the posterior columns, but normal sensory nerve conduction. By exome-sequencing we have identified the same p.Arg199Cys RNF170 mutation in an Ecuadorian family affected by an autosomal dominant late-onset progressive sensory ganglionopathy. Unlike the previously reported cases from Eastern Canada, affected members showed evidence of ganglionic/postganglionic involvement of the sensory peripheral nerves. Also, bilateral vestibular areflexia was identified in the index case, mimicking CANVAS. The index case (III-3, figure 1A) is a 57-year-old woman with onset of poor balance at the age of 47 years, followed by dysaesthesia and sensory loss in her feet and hands. At the age of 57 years she was referred for neurological evaluation, by which time she required a walking aid. Her past medical history was notable for rheumatic fever and gastro-oesophageal reflux. A sister had similar symptoms and her father and paternal grandmother both reported progressive …
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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) | 0.000 | 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 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| 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".