title: Histopathological findings in hereditary motor and sensory neuropathy of axonal type with onset in early childhood associated with mitofusin 2 mutations.
abstract: Neuropathologic abnormalities can be sufficiently characteristic to suggest the genetic basis of some hereditary neuropathies such as those associated with mutations in MPZ, GJB1, GDAP1, MTMR2, SH3TC2, PRX, FGD4, and LMNA. We analyzed the morphologic features of 9 sural nerve biopsies from 6 patients with mutations of mitofusin 2. All patients presented in early childhood with axonal neuropathies designated as mild or severe motor and sensory neuropathy. In all cases, there was a marked decrease in density of myelinated fibers, mainly of large diameter fibers. These changes were more marked in the second biopsies of 3 patients that were performed from 7 to 19 years after the first biopsies. Neurophysiologic findings were most suggestive of axonal degeneration, but some onion bulbs were present in all cases. Axonal mitochondria were smaller than normal, were round, and were abnormally aggregated. These changes may result from abnormal mitochondrial fusion and fission. The results suggest that these clinical and pathological features may be sufficiently characteristic to suggest the diagnosis of mitofusin 2-related neuropathy.
authors.affiliation: Laboratoire de Neurologie, Centre de Référence des Neuropathies Périphériques Rares, CHU de Limoges, Limoges, France. jean-michel.vallat@unilim.fr
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Vallat
authors.forename: Robert A
authors.initials: RA
authors.lastname: Ouvrier
authors.forename: John D
authors.initials: JD
authors.lastname: Pollard
authors.forename: Corinne
authors.initials: C
authors.lastname: Magdelaine
authors.forename: Danqing
authors.initials: D
authors.lastname: Zhu
authors.forename: Garth A
authors.initials: GA
authors.lastname: Nicholson
authors.forename: Simon
authors.initials: S
authors.lastname: Grew
authors.forename: Monique M
authors.initials: MM
authors.lastname: Ryan
authors.forename: Benoît
authors.initials: B
authors.lastname: Funalot
mesh_terms: D000328:Adult; D001369:Axons / Q000473:pathology* / Q000648:ultrastructure; D002648:Child; D002675:Child, Preschool; D005260:Female; D020558:GTP Phosphohydrolases; D015417:Hereditary Sensory and Motor Neuropathy / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008928:Mitochondria / Q000473:pathology / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000235:genetics*; D009154:Mutation; D013497:Sural Nerve / Q000473:pathology* / Q000648:ultrastructure; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human