Novel CACNB4 Variant Associated with a Case of Progressive Ataxia (P5.391)
Bibliographic record
Abstract
Objective: To describe a case of progressive ataxia associated with a novel mutation in CACNB4. Background: The Cav 2.1 (P/Q type Ca-channel) comprises of 4 subunits, α1A, β4, α2-δ, and γ. CACNB4 codes for the β4-subunit. A mutation in CACNB4 has been reported to cause idiopathic generalized epilepsy and episodic ataxia type 5 (OMIM 613855) and mutations in the α1A-subunit can cause Episodic ataxia type 2 (OMIM 108500 ) and Spinocerebellar Ataxia type 6 (OMIM 183086). Design/Methods: We report a 62 year-old French Canadian woman who presents with gradual onset of balance problems in her 40’s which has progressed without clear exacerbations. There is no family history of seizures or ataxia. Her neurological exam reveals ataxia, spasticity and peripheral neuropathy. She was investigated for causes of ataxia. Results: Neuroimaging was unremarkable. α-feto-protein, Vit E, ceruloplasmin, phytanic acid, Vit B12, very long chain fatty acids and TTG were normal. Next generation sequencing of an ataxia panel demonstrated a variant 1418G>A in CACNB4 resulting in an amino acid change p.Arg473His in the highly conserved carboxy tail. Her family members are in the process of being tested. Conclusions: Mutations in genes (CACNB4, CACNA1A) which code for Cav2.1, have previously been demonstrated to cause ataxia (EA5, EA2, SCA6). We present a novel variant in CACNB4, which is associated with a case of progressive ataxia, spasticity and peripheral neuropathy. This 1418G>A variant results in an amino acid change p. Arg473His in the highly conserved carboxy tail. The β4 subunit has two sites, which interact with the α1A subunit. One of these sites is the carboxy tail. We postulate that a potential pathogenic mechanism for this variant is a disruption in the interaction between the B4 and α1A-subunit.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.002 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.003 | 0.002 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.003 | 0.002 |
| 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".