Identification, clinical characterization, and molecular genetic studies of familial partial epilepsy with variable foci
Bibliographic record
Abstract
We identified two large French-Canadian (FC) pedigrees with idiopathic partial epilepsy. Family studies of over 500 members from these two families revealed over 63 individuals reported to have seizures or seizure-like histories. Pedigree analysis confirmed an autosomal dominant inheritance with reduced penetrance. Most of the affected individuals shared a number of clinical characteristics compatible with the definition of a novel genetic form of epilepsy syndrome. We termed it as familial partial epilepsy with variable foci (FPEVF), which was recently described by Scheffer et al. (1998) in one Australian family with eight possibly affected individuals. The most prominent clinical feature of FPEVF is the presence of variable seizure foci in different affected individuals within the same family. Most affected individuals in the two FC families present infrequent, brief, non-clustering, nocturnal, partial seizures. Age of onset is between 5 and 25 years. Affected individuals are neurologically intact without any detectable pathological lesion(s). These two families were then subjected to a full-scale molecular genetic study. No linkage to any known loci for idiopathic partial epilepsy was detected, including the suggested chromosome (Chr) 2q locus for FPEVF in the Australian FPEVF family, the Chr 20q13.2 and 15q24 loci for autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) and the Chr 10q locus for autosomal dominant temporal lobe epilepsy with auditory symptoms (ADTLEAS). Significant linkage (LOD score = 8.60) was detected with markers on Chr 22 q12 during a genome scan. Collaborating with a group from Australia, we confirmed another two FC families and two non-FC families with compatible linkage to the same locus and a cumulative LOD score of 14.79 with marker D22S689. The minimum candidate region of FPEVF has been finally defined to an interval of 3.8 cM between markers D22S 1163 and D22S 1686 on Chr 22q12. We proceeded to search for the gene mutation by directly sequencing the coding regions of all candidate genes within the FPEVF region, an interval of 5.04 Mb harboring approximately 100 known or predicted genes. So far, 77 candidate genes have been sequenced, and no mutation has yet been found. Since there is no known ion channel gene mapped to this region, FPEVF is probably the first non-ion channel gene causing human idiopathic epilepsy*. *After submission of this thesis for examination, Kalachikov et al. (2002) identified LGI1 (leucine-rich gene, glioma inactivated), a possible tumor suppressor, as the gene for ADTLEAS. This is the first evidence for a non-ion channel gene causing idiopathic epilepsy in humans.
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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 | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".