Novel spastic ataxia of Charlevoix-Saguenay gene compound heterozygous mutations in late onset autosomal recessive spastic ataxia of Charlevoix-Saguenay
Bibliographic record
Abstract
Objective To investigate the clinical features and laboratory results in a patient with late onset autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) carrying novel SACS (spastic ataxia of Charlevoix-Saguenay) gene heterozygous mutations. Methods A 26-year-old Chinese man developed since the age of 13 a progressive weakness and stiffness of his bilateral lower limbs and gait unsteadiness. He had pyramidal tract sign in his bilateral lower limbs, cerebellar ataxia and sensory-motor polyneuropathy, with hyperelastica and swan neck-like deformities of the fingers, pes cavus and hammer toes. Funduscopy and optical coherence tomography, brain and cervical MRI, conduction velocity of peripheral nerve, motor evoked potentials, visual and brainstem auditory evoked potentials, ultrasound of peripheral nerve, hips and legs MRI, electronystagmography, and targeted capture and next generation sequencing were performed. Results Funduscopy and optical coherence tomography revealed thickening of the retinal nerve fiber layer with unclear margined optic disc. MRI revealed symmetrical linear hypointensity lesions in the pons on T2 and T2 FLAIR weighted images, thickened bilateral cerebellar peduncles, and flattened and atrophied cervical and upper thoracic spinal cord. Nerve conduction studies showed sensory nerve action potentials were absent in four limbs, motor conduction velocity was slowed, amplitude of muscle response was significantly decreased in lower-limb nerves (decreased by 80%-100%) but normal in upper-limb nerves. Central motor conduction time of motor evoked potential was prolonged. Targeted capture and next generation sequencing revealed novel SACS compound heterozygous mutations, c. 12637_12638delGA (p.Glu4213ArgFs*3) and c. 11274_11276delAAC (p.Ile3758_Thr3759delinsMet) derived from each parent respectively, which were confirmed by Sanger sequencing analyses. Conclusions Recognizing ARSACS triad and its characteristics on fundus and brain MRI is helpful for correct diagnosis. Our findings expand the clinical and genetic spectrum of ARSACS. Key words: Spinocerebellar degenerations; Ataxia; Polyneuropathies; Magnetic resonance imaging; Mutation
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".