A novel homozygous MFN2 mutation associated with severe and atypical CMT2 phenotype

Giulia Iapadre, Giovanni Morana, Maria Stella Vari, Francesca Pinto, Paola Lanteri, Alessandra Tessa, Filippo Maria Santorelli, Pasquale Striano, Alberto Verrotti

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Charcot-Marie-Tooth (CMT) neuropathies represent the most common forms of inherited polyneuropathies. CMT2A, the axonal form, accounts for about one third of all CMT cases. Variants in the MFN2 gene have been recognized to be a major cause of CMT2A. To date, more than 100 pathogenetic mutations in MFN2 have been identified, leading to different neurological clinical spectrum, varying from hereditary neuropathies to more severe clinical phenotypes. Pathogenic variants in MFN2 mainly act in a dominant manner, although in a few sporadic or familial cases, homozygous or compound heterozygous mutations have been reported.

RESULTS: We describe a child carrying a novel homozygous MFN2 mutation leading to an early-onset sensorimotor axonal neuropathy with an atypical and severe phenotype.

CONCLUSION: The case highlights a very rare mechanism of inheritance for MFN2 mutations and expands the clinical and allelic variance of severe CMT2A phenotype. Moreover, it proposes the involvement of cerebellar peduncles observed at neuroimaging as a novel clue to suspect the diagnosis and address genetic testing.

Original languageEnglish
Pages (from-to)563-567
Number of pages5
JournalEuropean Journal of Paediatric Neurology
Volume22
Issue number3
DOIs
Publication statusPublished - May 2018

Fingerprint

Phenotype
Mutation
Tooth
Polyneuropathies
Genetic Testing
Neuroimaging
Genes

Keywords

  • Alleles
  • Charcot-Marie-Tooth Disease/diagnosis
  • Child
  • Female
  • GTP Phosphohydrolases/genetics
  • Genetic Testing
  • Homozygote
  • Humans
  • Mitochondrial Proteins/genetics
  • Mutation
  • Phenotype

Cite this

A novel homozygous MFN2 mutation associated with severe and atypical CMT2 phenotype. / Iapadre, Giulia; Morana, Giovanni; Vari, Maria Stella; Pinto, Francesca; Lanteri, Paola; Tessa, Alessandra; Santorelli, Filippo Maria; Striano, Pasquale; Verrotti, Alberto.

In: European Journal of Paediatric Neurology, Vol. 22, No. 3, 05.2018, p. 563-567.

Research output: Contribution to journalArticle

Iapadre, Giulia ; Morana, Giovanni ; Vari, Maria Stella ; Pinto, Francesca ; Lanteri, Paola ; Tessa, Alessandra ; Santorelli, Filippo Maria ; Striano, Pasquale ; Verrotti, Alberto. / A novel homozygous MFN2 mutation associated with severe and atypical CMT2 phenotype. In: European Journal of Paediatric Neurology. 2018 ; Vol. 22, No. 3. pp. 563-567.
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abstract = "BACKGROUND: Charcot-Marie-Tooth (CMT) neuropathies represent the most common forms of inherited polyneuropathies. CMT2A, the axonal form, accounts for about one third of all CMT cases. Variants in the MFN2 gene have been recognized to be a major cause of CMT2A. To date, more than 100 pathogenetic mutations in MFN2 have been identified, leading to different neurological clinical spectrum, varying from hereditary neuropathies to more severe clinical phenotypes. Pathogenic variants in MFN2 mainly act in a dominant manner, although in a few sporadic or familial cases, homozygous or compound heterozygous mutations have been reported.RESULTS: We describe a child carrying a novel homozygous MFN2 mutation leading to an early-onset sensorimotor axonal neuropathy with an atypical and severe phenotype.CONCLUSION: The case highlights a very rare mechanism of inheritance for MFN2 mutations and expands the clinical and allelic variance of severe CMT2A phenotype. Moreover, it proposes the involvement of cerebellar peduncles observed at neuroimaging as a novel clue to suspect the diagnosis and address genetic testing.",
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T1 - A novel homozygous MFN2 mutation associated with severe and atypical CMT2 phenotype

AU - Iapadre, Giulia

AU - Morana, Giovanni

AU - Vari, Maria Stella

AU - Pinto, Francesca

AU - Lanteri, Paola

AU - Tessa, Alessandra

AU - Santorelli, Filippo Maria

AU - Striano, Pasquale

AU - Verrotti, Alberto

N1 - Copyright © 2018 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

PY - 2018/5

Y1 - 2018/5

N2 - BACKGROUND: Charcot-Marie-Tooth (CMT) neuropathies represent the most common forms of inherited polyneuropathies. CMT2A, the axonal form, accounts for about one third of all CMT cases. Variants in the MFN2 gene have been recognized to be a major cause of CMT2A. To date, more than 100 pathogenetic mutations in MFN2 have been identified, leading to different neurological clinical spectrum, varying from hereditary neuropathies to more severe clinical phenotypes. Pathogenic variants in MFN2 mainly act in a dominant manner, although in a few sporadic or familial cases, homozygous or compound heterozygous mutations have been reported.RESULTS: We describe a child carrying a novel homozygous MFN2 mutation leading to an early-onset sensorimotor axonal neuropathy with an atypical and severe phenotype.CONCLUSION: The case highlights a very rare mechanism of inheritance for MFN2 mutations and expands the clinical and allelic variance of severe CMT2A phenotype. Moreover, it proposes the involvement of cerebellar peduncles observed at neuroimaging as a novel clue to suspect the diagnosis and address genetic testing.

AB - BACKGROUND: Charcot-Marie-Tooth (CMT) neuropathies represent the most common forms of inherited polyneuropathies. CMT2A, the axonal form, accounts for about one third of all CMT cases. Variants in the MFN2 gene have been recognized to be a major cause of CMT2A. To date, more than 100 pathogenetic mutations in MFN2 have been identified, leading to different neurological clinical spectrum, varying from hereditary neuropathies to more severe clinical phenotypes. Pathogenic variants in MFN2 mainly act in a dominant manner, although in a few sporadic or familial cases, homozygous or compound heterozygous mutations have been reported.RESULTS: We describe a child carrying a novel homozygous MFN2 mutation leading to an early-onset sensorimotor axonal neuropathy with an atypical and severe phenotype.CONCLUSION: The case highlights a very rare mechanism of inheritance for MFN2 mutations and expands the clinical and allelic variance of severe CMT2A phenotype. Moreover, it proposes the involvement of cerebellar peduncles observed at neuroimaging as a novel clue to suspect the diagnosis and address genetic testing.

KW - Alleles

KW - Charcot-Marie-Tooth Disease/diagnosis

KW - Child

KW - Female

KW - GTP Phosphohydrolases/genetics

KW - Genetic Testing

KW - Homozygote

KW - Humans

KW - Mitochondrial Proteins/genetics

KW - Mutation

KW - Phenotype

U2 - 10.1016/j.ejpn.2017.12.020

DO - 10.1016/j.ejpn.2017.12.020

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JO - European Journal of Paediatric Neurology

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