Late onset Leigh syndrome and ataxia due to a T to C mutation at bp 9,185 of mitochondrial DNA
Bibliographic record
Abstract
A T-to-C missense mutation at nucleotide position 9,185 in the protein-coding ATP6 gene of the mitochondrial genome was present at high heteroplasmy in members of a Canadian family with Leigh syndrome with predominant ataxia and peripheral neuropathy. This mutation results in the substitution of a proline residue for an evolutionary-conserved leucine at position of amino acid 220 near the carboxyl terminus of the mitochondrial protein. The index patient and brother, who had an identical clinical presentation, had >90% mutant mtDNA in cultured skin fibroblasts, lymphocytes, and whole blood. Their mother and a maternal uncle, symptomatic with a peripheral neuropathy alone, had 86% and 85% heteroplasmy, respectively. Symptomatic maternal cousins with early onset revealed 90% and 91% mutant mtDNA in all tissues analyzed. Studies of lymphoblasts from the asymptomatic maternal grandmother and eldest brother of the proband were heteroplasmic for mutant mtDNA with 56% and 17%, respectively. Biochemical analysis demonstrated normal respiratory chain enzyme activity in muscle and fibroblasts, normal ATP synthesis, but reduced oligomycin-sensitive H(+)ATPase in cultured lymphoblast mitochondria. We propose that the 9,185T > C mtDNA mutation is pathogenic even though the initial phenotype is mild and the biochemical phenotype not easily detectable.
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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".