title: The EGR2 gene is involved in axonal Charcot-Marie-Tooth disease.
abstract: OBJECTIVE
  A three-generation family affected by axonal Charcot-Marie-Tooth disease (CMT) was investigated with the aim of discovering genetic defects and to further characterize the phenotype.
  
  
  METHODS
  The clinical, nerve conduction studies and muscle magnetic resonance images of the patients were reviewed. A whole exome sequencing was performed and the changes were investigated by genetic studies, in silico analysis and luciferase reporter assays.
  
  
  RESULTS
  A novel c.1226G>A change (p.R409Q) in the EGR2 gene was identified. Patients presented with a typical, late-onset axonal CMT phenotype with variable severity that was confirmed in the ancillary tests. The in silico studies showed that the residue R409 is an evolutionary conserved amino acid. The p.R409Q mutation, which is predicted as probably damaging, would alter the conformation of the protein slightly and would cause a decrease of gene expression.
  
  
  CONCLUSIONS
  This is the first report of an EGR2 mutation presenting as an axonal CMT phenotype with variable severity. This study broadens the phenotype of the EGR2-related neuropathies and suggests that the genetic testing of patients suffering from axonal CMT should include the EGR2 gene.
authors.affiliation: Department of Neurology, Hospital Universitari i Politècnic La Fe, Valencia, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Valencia, Spain.|Department of Medicine, University of Valencia, Valencia, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Sevilla
authors.affiliation: Department of Neurology, Hospital Universitari i Politècnic La Fe, Valencia, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Sivera
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Valencia, Spain.|Program in Genetics and Rare Diseases and IBV/CSIC Associated Unit, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Martínez-Rubio
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Valencia, Spain.|Program in Genetics and Rare Diseases and IBV/CSIC Associated Unit, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Lupo
authors.affiliation: Department of Clinical Neurophysiology, Hospital Universitari i Politècnic La Fe, Valencia, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Chumillas
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Valencia, Spain.|Program in Genetics and Rare Diseases and IBV/CSIC Associated Unit, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Calpena
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Valencia, Spain.|Program in Computational Genomics, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Dopazo
authors.affiliation: Department of Neurology, Hospital Universitari i Politècnic La Fe, Valencia, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Valencia, Spain.|Department of Medicine, University of Valencia, Valencia, Spain.
authors.forename: J J
authors.initials: JJ
authors.lastname: Vílchez
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Valencia, Spain.|Program in Genetics and Rare Diseases and IBV/CSIC Associated Unit, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Palau
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Valencia, Spain.|Program in Genetics and Rare Diseases and IBV/CSIC Associated Unit, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.|Department of Genetics, Universitat de València, Valencia, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Espinós
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001369:Axons / Q000473:pathology; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D051767:Early Growth Response Protein 2 / Q000235:genetics*; D059472:Exome; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: C497326:EGR2 protein, human; D051767:Early Growth Response Protein 2
keywords: Charcot−Marie−Tooth disease; EGR2 gene; hereditary motor sensory neuropathy; whole exome sequencing