Search for mutations in the EGR2 corepressor proteins, NAB1 and NAB2, in human peripheral neuropathies

Neurogenetics. 2002 Mar;4(1):37-41. doi: 10.1007/s10048-001-0124-2.

Abstract

EGR2/Krox-20, a Cys2-His2 zinc finger transcription factor, plays an essential role in the regulation of myelination in the peripheral nervous system. Dominant and recessive mutations in EGR2 are associated with peripheral myelinopathies, such as Charcot-Marie-Tooth disease type 1, Dejerine-Sottas syndrome, and congenital hypomyelinating neuropathy. One recessive mutation (I268N) is known to affect the inhibitory domain that binds the NAB transcriptional corepressors, NAB1 and NAB2. This mutation abolishes the interaction of EGR2 with the NAB corepressors and thereby increases transcriptional activity. Therefore, we hypothesized that mutations in the EGR2-interacting domains of NAB1 and NAB2 might be associated with the pathogenesis of inherited peripheral neuropathies in currently unexplained cases. However, screening 87 such cases failed to identify any disease-causing mutations within the EGR2-interacting domains of either NAB1 or NAB2. A further mutation analysis of the complete coding regions of NAB1 and NAB2 in these genomic DNA samples did not uncover any disease-causing mutation. Therefore, our analysis indicates that mutations in the human NABI and NAB2 genes are most likely not involved in the pathogenesis of peripheral neuropathies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Mutational Analysis
  • DNA-Binding Proteins / metabolism*
  • Early Growth Response Protein 2
  • Humans
  • Mutation
  • Neoplasm Proteins*
  • Peripheral Nervous System Diseases / genetics*
  • RNA Splice Sites / genetics
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism*
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • EGR2 protein, human
  • Early Growth Response Protein 2
  • NAB1 protein, human
  • NAB2 protein, human
  • Nab1 protein, mouse
  • Neoplasm Proteins
  • RNA Splice Sites
  • Repressor Proteins
  • Transcription Factors