title: The modifying effect a PMP22 deletion in a family with Charcot-Marie-Tooth type 1 neuropathy due to an EGR2 mutation.
abstract: BACKGROUND
  Mutations of both the PMP22 and EGR2 genes cause Charcot-Marie-Tooth (CMT) disease type 1. Deletion of the PMP22 gene, results in hereditary neuropathy with liability to pressure palsies. More publications exist about the interaction of PMP22 duplication and other CMT-causing gene mutations. In these cases the intrafamiliar discordant phenotypes draw the attention to the possible role of modifying genes. The gene-gene interactions between the PMP22 and EGR2 genes are not well understood.
  
  
  METHODS
  We report two brothers with late onset CMT1 due to a c. 1142 G>A (Arg381His) heterozygous substitution in the EGR2 gene. Additionally, the older brother with the less severe symptoms harbored the PMP22 gene deletion also.
  
  
  CONCLUSIONS
  The coexistence of the two genetic alterations did not aggravate the clinical symptoms. Moreover, the PMP22 deletion appeared to have a beneficial modifying effect, thus implying potential gene-gene interaction of PMP22 and EGR2. PMP22 deletion may increase Schwann cells proliferation and compensate the dominant-negative effect of the Arg381 His substitution in the EGR2 gene.
authors.forename: Viktória
authors.initials: V
authors.lastname: Reményi
authors.forename: Gabriella
authors.initials: G
authors.lastname: Inczédy-Farkas
authors.forename: Anikó
authors.initials: A
authors.lastname: Gál
authors.forename: Benjamin
authors.initials: B
authors.lastname: Bereznai
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Pál
authors.forename: Veronica
authors.initials: V
authors.lastname: Karcagi
authors.forename: Ferenc
authors.initials: F
authors.lastname: Mechler
authors.forename: Mária Judit
authors.initials: MJ
authors.lastname: Molnár
mesh_terms: D000328:Adult; D017668:Age of Onset; D019943:Amino Acid Substitution; D001120:Arginine; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D051767:Early Growth Response Protein 2 / Q000235:genetics*; D017353:Gene Deletion; D006639:Histidine; D006801:Humans; D008297:Male; D008475:Median Nerve / Q000503:physiopathology; D008875:Middle Aged; D009185:Myelin Proteins / Q000235:genetics*; D009431:Neural Conduction; D010543:Peroneal Nerve / Q000503:physiopathology; D013497:Sural Nerve / Q000473:pathology / Q000503:physiopathology; D014459:Ulnar Nerve / Q000503:physiopathology
chemical_list: C497326:EGR2 protein, human; D051767:Early Growth Response Protein 2; D009185:Myelin Proteins; C073687:PMP22 protein, human; D006639:Histidine; D001120:Arginine