Neuropathy due to impaired axonal transport of non-fragmented mitochondria in MYH14 mutation carriers
Notice bibliographique
Résumé
With interest we read the article by Almutawa et al. about a family with neuropathy, hypoacusis, and foot deformity, being attributed to the heterozygous variant R941L in MYH14 [[1]Almutawa W. Smith C. Sabouny R. Smit R.B. Zhao T. Wong R. Lee-Glover L. Desrochers-Goyette J. Ilamathi H.S. Suchowersky O. Germain M. Mains P.E. Parboosingh J.S. Pfeffer G. Innes A.M. Shutt T.E. Care4Rare Canada ConsortiumThe R941L mutation in MYH14 disrupts mitochondrial fission and associates with peripheral neuropathy.EBioMedicine. 2019; 45: 379-392https://doi.org/10.1016/j.ebiom.2019.06.018Summary Full Text Full Text PDF Scopus (16) Google Scholar]. Neuropathy was attributed to impaired fission of mitochondria resulting in oversized organelles inappropriate for retrograde axonal transportation [1Almutawa W. Smith C. Sabouny R. Smit R.B. Zhao T. Wong R. Lee-Glover L. Desrochers-Goyette J. Ilamathi H.S. Suchowersky O. Germain M. Mains P.E. Parboosingh J.S. Pfeffer G. Innes A.M. Shutt T.E. Care4Rare Canada ConsortiumThe R941L mutation in MYH14 disrupts mitochondrial fission and associates with peripheral neuropathy.EBioMedicine. 2019; 45: 379-392https://doi.org/10.1016/j.ebiom.2019.06.018Summary Full Text Full Text PDF Scopus (16) Google Scholar, 2Ueda E. Ishihara N. Mitochondrial hyperfusion causes neuropathy in a fly model of cmt2a.EMBO Rep. 2018; 19 (pii: e46502)https://doi.org/10.15252/embr.201846502Crossref Scopus (4) Google Scholar]. We have the following concerns. A main shortcoming of the study is that no nerve biopsies were carried out. Assuming that neuropathy was due to impaired fission and thus reduced axonal transport of mitochondria [[1]Almutawa W. Smith C. Sabouny R. Smit R.B. Zhao T. Wong R. Lee-Glover L. Desrochers-Goyette J. Ilamathi H.S. Suchowersky O. Germain M. Mains P.E. Parboosingh J.S. Pfeffer G. Innes A.M. Shutt T.E. Care4Rare Canada ConsortiumThe R941L mutation in MYH14 disrupts mitochondrial fission and associates with peripheral neuropathy.EBioMedicine. 2019; 45: 379-392https://doi.org/10.1016/j.ebiom.2019.06.018Summary Full Text Full Text PDF Scopus (16) Google Scholar], it is conceivable that nerve biopsy may show paucity of mitochondria within motor and sensory axons and in nerve terminals. Concerning mitochondrial functions, it is desirable to confirm normal function of the respiratory chain by appropriate biochemical investigations [[3]Amiott E.A. Lott P. Soto J. Kang P.B. McCaffery J.M. DiMauro S. Abel E.D. Flanigan K.M. Lawson V.H. Shaw J.M. Mitochondrial fusion and function in charcot-marie-tooth type 2A patient fibroblasts with mitofusin 2 mutations.Exp Neurol. 2008; 211: 115-127Crossref PubMed Scopus (72) Google Scholar]. A further shortcoming is that neuropathy was classified as axonal [[1]Almutawa W. Smith C. Sabouny R. Smit R.B. Zhao T. Wong R. Lee-Glover L. Desrochers-Goyette J. Ilamathi H.S. Suchowersky O. Germain M. Mains P.E. Parboosingh J.S. Pfeffer G. Innes A.M. Shutt T.E. Care4Rare Canada ConsortiumThe R941L mutation in MYH14 disrupts mitochondrial fission and associates with peripheral neuropathy.EBioMedicine. 2019; 45: 379-392https://doi.org/10.1016/j.ebiom.2019.06.018Summary Full Text Full Text PDF Scopus (16) Google Scholar] although there was only borderline CMAP reduction, thus not fulfilling the criteria for axonal degeneration [[4]Yadegari S. Nafissi S. Kazemi N. Comparison of electrophysiological findings in axonal and demyelinating guillain-barre syndrome.Iran J Neurol. 2014; 13: 138-143Google Scholar]. Additionally, we should know which nerves were involved, if involvement was symmetric/asymmetric, if there was upper/lower limb predominance, and if there was distal, proximal, or diffuse distribution of the lesions. We also should know if motor and sensory nerves were equally affected and if there was involvement of the autonomic fibres. Missing is an explanation of hypoacusis. We should know if it was due to sensory or neuronal involvement, which could be best achieved by application of acoustically-evoked potentials [[5]Abou-Elew M.H. Hosni N.A. Obaid E.A. Ewida A.H. The N3 potential and the efferent cochlear pathway in profound sensorineural hearing loss.J Laryngol Otol. 2017; 131: 334-340Google Scholar]. We should know why among the cranial nerves only the acoustic nerve was affected and why this cranial nerve was affected long before the onset of peripheral neuropathy. No funding was received Author contribution: JF: design, literature search, discussion, first draft, critical comments Informed consent: was obtained The study was approved by the institutional review board None. The R941L mutation in MYH14 disrupts mitochondrial fission and associates with peripheral neuropathyAs impairments in mitochondrial fission cause peripheral neuropathy, this insight into the function of NMIIC likely explains the peripheral neuropathy phenotype associated with the R941L mutation. Full-Text PDF Open Access
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».