title: Severe early-onset axonal neuropathy with homozygous and compound heterozygous MFN2 mutations.
abstract: OBJECTIVE
  Severe early-onset axonal neuropathy (SEOAN) is a heterogeneous phenotype first delineated by Ouvrier et al., characterized by progressive axonal degeneration with gait problems often progressing to wheelchair requirement and later respiratory involvement. Most cases are sporadic single cases. Some have heterozygous mitofusin 2 (MFN2) mutations, many of which are de novo dominant mutations. The aim of this study was to investigate the mode of inheritance in three individuals with severe early-onset axonal neuropathy and homozygous or compound heterozygous MFN2 mutations.
  
  
  METHODS
  The clinical and molecular findings in the parents of three individuals with SEOAN with homozygous or compound heterozygous MFN2 mutations were examined.
  
  
  RESULTS
  All parents were asymptomatic or mildly symptomatic with some signs of peripheral neuropathy indicating a minimal phenotype. Two had hearing problems. All parents carried the relevant single base (heterozygous) MFN2 variations.
  
  
  CONCLUSIONS
  Severe early-onset axonal neuropathy due to MFN2 mutations can present as an apparently recessively inherited neuropathy but the minimal phenotype in the parents suggests a semi-dominant mechanism.
authors.affiliation: Molecular Medicine Laboratory and ANZAC Research Institute, Clinical Sciences Building, Concord Hospital, NSW 2139, Australia. garthn@med.usyd.edu.au
authors.forename: G A
authors.initials: GA
authors.lastname: Nicholson
authors.forename: C
authors.initials: C
authors.lastname: Magdelaine
authors.forename: D
authors.initials: D
authors.lastname: Zhu
authors.forename: S
authors.initials: S
authors.lastname: Grew
authors.forename: M M
authors.initials: MM
authors.lastname: Ryan
authors.forename: F
authors.initials: F
authors.lastname: Sturtz
authors.forename: J-M
authors.initials: JM
authors.lastname: Vallat
authors.forename: R A
authors.initials: RA
authors.lastname: Ouvrier
mesh_terms: D000328:Adult; D017668:Age of Onset; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D020558:GTP Phosphohydrolases; D005799:Genes, Dominant / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006319:Hearing Loss, Sensorineural / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010525:Peripheral Nerves / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D014855:Wallerian Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology
chemical_list: D005819:Genetic Markers; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human