Response to “Pathogenicity of Variant m.13528A>G in MT-ND5 in Leber’s Hereditary Optic Neuropathy Is Unsupported”
Bibliographic record
Abstract
We thank Finsterer and Mehri [1] for their interest in our case report describing a 57year-old male patient with the m.13528A>G, p. (Thr398Ala) mutation at the ND5 gene diagnosed with Leber hereditary optic neuropathy (LHON).The CARE Checklist has been completed for the case report, attached as online supplementary material (for all online suppl.material, see https://doi.org/10.1159/000535021).The assertion that "the variant reported by Batandier et al.[2] was m.13528G>A" by the authors is incorrect as the mutation was indeed described as 13528A>G by Batandier et al. [2], consistent with what we reported in our case report.This mutation was present at 100% homoplasmy in our patient, and moreover, McKenzie et al. [3] and Petruzzella et al. [4] reported this mutation to be homoplasmic.Therefore, the assertion that "the heteroplasmy rate is 100%" by Finsterer and Mehri [1] is inaccurate.McKenzie et al.[3] analyzed the m.13528A>G mutation in a patient with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes, and demonstrated (I) increased lactate production and (II) decreased mitochondrial membrane potential, resulting in complex I dysfunction.Petruzzella et al. [4] performed an elegant biochemical analysis in an LHON patient with this mutation where they demonstrated (I) an increase in reactive oxygen species formation and (II) complex I deficiency as characterized by a decrease in adenosine triphosphate production.We acknowledge that neither study definitively implicates the m.13528A>G mutation in causing LHON, but it is inaccurate to assert that there is "an absence of evidence of respiratory complex-I deficiency" in the context of this mutation.We agree that further biochemical studies are warranted
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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 | 0.001 | 0.007 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.020 | 0.015 |
| Insufficient payload (model declined to judge) | 0.011 | 0.006 |
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".