Platform Highlights Session A 4:30 p.m.-6:00 p.m.
Bibliographic record
Abstract
Abstract Samuel F. Berkovic 1,2 , L. M. Dibbens 3 , A. Oshlack 4 , J. D. Silver 4,5 , M. Katerelos 6 , D. F. Vears 1 , J. Stankovich 4,7 , E. Andermann 8 , F. Andermann 8 , B. L. Hodgson 3 , M. A. Bayly 3 , J. C. Mulley 3 , G. K. Smyth 4 , D. A. Power 2,6 and M. Bahlo 4 ( 1 Epilepsy Research Centre and Department of Medicine, University of Melbourne, Heidelberg West, VIC, Australia ; 2 Departments of Neurology and Anatomical Pathology, Austin Health, Heidelberg, VIC, Australia ; 3 Department of Genetic Medicine, Women's and Children's Hospital, Adelaide, SA, Australia ; 4 The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia ; 5 Department of Mathematics and Statistics, University of Melbourne, Parkville, VIC, Australia ; 6 Burnet Institute at Austin, Austin Health, Heidelberg, VIC, Australia ; 7 Menzies Research Institute, University of Tasmania, Hobart, TAS, Australia and 8 Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital McGill University, Montreal, QC, Canada ) Rationale: Action myoclonus renal failure (AMRF) syndrome is a lethal inherited form of progressive myoclonus epilepsy associated with renal failure. It typically presents at 15 – 25 years with neurological symptoms (tremor, action myoclonus, seizures and later ataxia), or proteinuria evolving into renal failure requiring dialysis or transplantation. The autosomal recessive gene defect underlying AMRF was unknown and the lack of large pedigrees and lethality of the disorder precluded a conventional mapping strategy. Methods: We studied three Australian patients and their families: case A of Turkish-Cypriot origin whose parents were first cousins, and cases B and C whose ancestors came from different regions of Britain and no inbreeding loops were known for either family. Using SNP chips and a novel mapping strategy, homozygosity mapping of a known consanguineous case was conducted and then combined with analysis of affected and unaffected siblings in the other families. Results: Homozygosity mapping using all three cases identified a 5.3 cM critical region on chromosome 4 and a second 3.0 cM region on chromosome 20. Microsatellite analysis in these regions excluded the chromosome 20 locus and leaving the chromosome 4 locus as the region of interest. Microarray expression analysis of the two living AMRF patients and their unaffected same sex siblings as controls identified a lysosomal protein as the likely candidate. Sequencing revealed mutations predicted to truncate the protein in all three patients and a subsequent family. Western blotting showed absent expression of this lysosomal membrane protein in lymphocytes. Conclusions: Using only 3 affected individuals, we have identified the gene for this rare form of progressive myoclonus epilepsy. This will allow for earlier diagnosis of this condition and provides new insights into the biology of this disorder. This work was supported by a grant from the Australian National Health and Medical Research Council.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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; both teacher heads agree on what is shown here.
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".