Identification of ALS5/SPG11/ <i>KIAA1840</i> Mutations in Patients with Autosomal Recessive Form of Charcot-Marie-Tooth Disease Type 2 (S44.002)
Bibliographic record
Abstract
Objective: This study focused on the ALS5/SPG11/KIAA1840 screening in 28 unrelated pedigrees with autosomal recessive axonal form of Charcot-Marie-Tooth disease (ARCMT2), recruited in Italy, Brazil, Canada, England, Iran, and Japan. Background: Mutations in the ALS5/SPG11/KIAA1840 gene are common cause of autosomal recessive form of hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) and account for approximately 40[percnt] of autosomal recessive juvenile amyotrophic lateral sclerosis (ARJALS). We extended the genetic analyses of ALS5/SPG11/KIAA1840 to CMT patients, especially those with the AR axonal form. Design/Methods: The diagnosis was based on clinical findings and familiar history. Clinical and instrumental functional analyses consist of neurological assessment, neuroimaging, electroneurographic assay, and sural nerve biopsy. Molecular studies include linkage analysis, Sanger sequencing, RFLP analysis, and bioinformatics. Results: All known ARCMT2 loci, genes causing ARHSP with TCC and genes causing ARCMT2, as well as the causative gene of peripheral neuropathy with or without agenesis of the corpus callosum were screened out. Linkage study of all families showed homozygous haplotypes and produced positive logarithm of odds score in all affected subjects. Sanger sequencing identified 15 ALS5/SPG11/KIAA1840 pathological mutations in 12 families. All pathological sequence changes were absent in controls. Two mutations were never reported before and in silico analysis predicted their pathogenetic effect. Co-segregation of each mutation with the disease was confirmed. Conclusions: Our results indicate that ALS5/SPG11/KIAA1840 is the causative gene of a wide spectrum of clinical features, including ARCMT2.
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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 | 0.000 |
| 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 | 0.000 |
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".