Acute optic neuropathy associated with a novel MFN2 mutation

Leonardi, Luca; Marcotulli, Christian; Storti, Eugenia; Tessa, Alessandra; Serrao, Mariano; Parisi, Vincenzo; Santorelli, Filippo M.; Pierelli, Francesco; Casali, Carlo

doi:10.1007/s00415-015-7756-x

Cited by 20 publications

(14 citation statements)

References 11 publications

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“…Mutated forms of MFN2 are all known to cause human disease with phenotypes such as encephalopathy, 2 peripheral neuropathy, 6 and optic atrophy. 2,[9][10][11] MFN2 is essential for the transport of mitochondria along axons such as for several other intracellular pathways (i.e. cell cycle progression, maintenance of mitochondrial bioenergetics, apoptosis, and autophagy).…”

Section: Discussionmentioning

confidence: 99%

“…Bombelli et al (2014) 10 reported three more cases of CMT2A and optic atrophy, vocal cord palsy, and auditory impairment. Leonardi et al (2015) 11 described a case of a 40 years old Caucasian male with CMT2A and a heterozygous c.775C [T (p. Arg259Cys)] mutation in MFN2 with an acute-onset optic neuropathy: the patient complained visual deterioration over the entire visual field with a rapid progression within a few hours without significant ocular pain. Ando et al (2017) 6 described a large case study on 1334 unrelated Japanese patients/families with clinically suspected CMT and reported that four patients with MFN2 mutations showed CMT2A with optic atrophy.…”

Section: Discussionmentioning

confidence: 99%

“…5 Repeated clinical observation of these features has led to several specifically designated subtypes of CMT. 6 Literature data show that optic atrophy in CMT2A has a subacute onset and patients develop central scotoma and color vision defects; visual acuity becomes gradually low and fundus examination shows pale optic disk; over the course of several years most individuals experience recovery of visual acuity, color vision 2,[7][8][9][10][11] We describe, for the first time, a CMT2A patient harboring a frameshift mutation in MFN2 who presented a bilateral progressive optic atrophy, with a normal visual acuity, normal color perception and bilateral severe concentric narrowing of the visual field.…”

Section: Introductionmentioning

confidence: 99%

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<p>CMT2A Harboring Mitofusin 2 Mutation with Optic Nerve Atrophy and Normal Visual Acuity</p>

Guerriero¹,

D’Oria²,

Rossetti³

et al. 2020

IMCRJ

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Charcot-Marie-Tooth (CMT) constitutes a group of heterogeneous hereditary motor and sensor neuropathies. Mutations in mitofusin-2 (MFN2) cause CMT type 2A by altering mitochondrial fusion and trafficking along with the axonal microtubule system. In literature patients presenting with CMT2A are reported as having a subacute onset of optic atrophy associated with central scotoma and color vision defects. We report on the clinical and genetic findings in a 40 years-old Caucasian woman presenting with CMT type 2A and MFN2 mutation (c.2258duplT/p.Leu753fs) who presented bilateral progressive optic atrophy with bilateral severe concentric narrowing of the visual field but normal visual acuity and color vision. This is the first report that describes such phenotypical manifestation of an MFN2 mutation suggesting that the molecular mechanisms underlying the mitofusin-2 function alteration at optic nerve need to be investigated further.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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<p>CMT2A Harboring Mitofusin 2 Mutation with Optic Nerve Atrophy and Normal Visual Acuity</p>

Guerriero¹,

D’Oria²,

Rossetti³

et al. 2020

IMCRJ

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“…Both autosomal dominant and autosomal recessive inheritance of these mutations, as well as sporadic new mutations have been described (133). Furthermore, truncation mutations in MFN2 have been shown to be responsible for hereditary motor sensory neuropathy type VI (HSMN VI), a rare early-onset axonal type of CMT associated with bilateral sub-acute, sometimes improved spontaneously, or acute optic neuropathy (11,31,(134)(135)(136). Although symptoms and disease severity are heterogeneous, the frequency of MFN2 mutations was shown to be significantly higher among severely affected patients with CMT2A (137,138).…”

Section: Afg3l2 Heterozygous Missense Mutations In the Afg3l2mentioning

confidence: 99%

Μitochondrial Membrane Dynamics and Inherited Optic Neuropathies

Bagli

Zikou

Agnantis

et al. 2017

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Abstract. Inherited optic neuropathies are a genetically diverse group of disorders mainly characterized by visual loss and optic atrophy. Since the first recognition of Leber's hereditary optic neuropathy, several genetic defects altering primary mitochondrial respiration have been proposed to contribute to the development of syndromic and nonsyndromic optic neuropathies. Moreover, the genomics and imaging revolution in the past decade has increased diagnostic efficiency and accuracy, allowing recognition of a link between mitochondrial dynamics machinery and a broad range of inherited neurodegenerative diseases involving the optic nerve. Mutations of novel genes modifying mainly the balance between mitochondrial fusion and fission have been shown to lead to overlapping clinical phenotypes ranging from isolated optic atrophy to severe, sometimes lethal multisystem disorders, and are reviewed herein. Given the particular vulnerability of retinal ganglion cells to mitochondrial dysfunction, the accessibility of the eye as a part of the central nervous system and improvements in technical imaging concerning assessment of the retinal nerve fiber layer, optic nerve evaluation becomes critical -even in asymptomatic patients -for correct diagnosis, understanding and early treatment of these complex and enigmatic clinical entities.Mitochondria represent a tubular and branched membrane system playing a fundamental role in several cellular processes required for the development and maintenance of an organism, such as metabolism, apoptosis, ion buffering and autophagy (1-3). They reveal a high degree of interconnectivity and plasticity, mainly dictated by metabolic status and developmental stage (4) and, therefore, a constant state of mitochondrial network flux is fundamental. This dynamic state is achieved through mitochondrial dynamics, a complex machinery of highly conserved mechanisms, including mitochondrial fusion, fission, transport, interorganellar communication and mitochondrial quality control (i.e. mitophagy), tuned to a variety of signals and stimuli (5-7), and well-orchestrated by specific intracellular proteins.The morphology and intracellular distribution of mitochondria vary significantly between tissues and cell types, being enriched in areas of increased metabolic demand, such as neurons, especially the presynaptic and postsynaptic terminals (8). Accordingly, it is not surprising that the pathogenic mechanism of various neurodegenerative diseases is established through an underlying deficiency of mitochondrial energy metabolism (9). However, in recent years it has been shown that impairment of mitochondrial dynamics also leads to synaptic dysfunction, dendritic and axonal degeneration and consequently to neurodegeneration (10,11). In this respect, restoration of mitochondrial function has become, for some time now, the priority target of novel neuroprotective strategies (12).Mitochondrial membrane dynamics, and more specifically fission and fusion, are indispensable for mitochondrial distribution and hom...

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“…However, phenotypical variation is also noted regardless of the type or position of the MFN2 mutation. Late‐onset mild sensory and motor symptoms in all limbs and peripheral neuropathy complicated with additional features such as multiple lipomatosis optic atrophy vocal cord palsy, auditory impairment, or pyramidal signs can be seen. Some patients show peripheral neuropathy with predominant sensory loss which mimics hereditary sensory autonomic neuropathy (HSAN).…”

Section: Introductionmentioning

confidence: 99%

Late‐onset hereditary sensory and autonomic neuropathy expands the phenotypic spectrum ofMFN2‐related diseases

Jun

Meng

et al. 2018

Neuropathology

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Mutations in the Mitofusin 2 (MFN2) gene have been identified in patients with autosomal dominant axonal motor and sensory neuropathy or Charcot-Marie-Tooth 2A (CMT2A). Here we describe clinical and pathological changes in an adult patient with sporadic hereditary sensory and autonomic neuropathy (HSAN) due to an MFN2 mutation. The patient was a 53-year-old man who had sensory involvement and anhidrosis in all limbs without motor features. The electrophysiological assessment documented severe axonal sensory neuropathy. The sural nerve biopsy confirmed the electrophysiological findings, revealing severe loss of myelinated and unmyelinated fibers with regeneration clusters. Genetic analysis revealed the previously identified mutation c.776 G > A in MFN2. Our report expands the phenotypic spectrum of MFN2-related diseases. Sequencing of MFN2 should be considered in all patients presenting with late-onset HSAN.

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Acute optic neuropathy associated with a novel MFN2 mutation

Cited by 20 publications

References 11 publications

<p>CMT2A Harboring Mitofusin 2 Mutation with Optic Nerve Atrophy and Normal Visual Acuity</p>

<p>CMT2A Harboring Mitofusin 2 Mutation with Optic Nerve Atrophy and Normal Visual Acuity</p>

Μitochondrial Membrane Dynamics and Inherited Optic Neuropathies

Late‐onset hereditary sensory and autonomic neuropathy expands the phenotypic spectrum ofMFN2‐related diseases

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