Peripheral nerve demyelination caused by a mutant Rho GTPase guanine nucleotide exchange factor, frabin/FGD4

Am J Hum Genet. 2007 Jul;81(1):158-64. doi: 10.1086/518770. Epub 2007 May 24.


GTPases of the Rho subfamily are widely involved in the myelination of the vertebrate nervous system. Rho GTPase activity is temporally and spatially regulated by a set of specific guanine nucleotide exchange factors (GEFs). Here, we report that disruption of frabin/FGD4, a GEF for the Rho GTPase cell-division cycle 42 (Cdc42), causes peripheral nerve demyelination in patients with autosomal recessive Charcot-Marie-Tooth (CMT) neuropathy. These data, together with the ability of frabin to induce Cdc42-mediated cell-shape changes in transfected Schwann cells, suggest that Rho GTPase signaling is essential for proper myelination of the peripheral nervous system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Charcot-Marie-Tooth Disease / genetics*
  • Charcot-Marie-Tooth Disease / pathology
  • Child
  • Demyelinating Diseases / genetics*
  • Demyelinating Diseases / pathology
  • Female
  • Humans
  • Male
  • Microfilament Proteins / analysis
  • Microfilament Proteins / genetics*
  • Molecular Sequence Data
  • Mutation
  • Myelin Sheath / enzymology*
  • Myelin Sheath / pathology
  • Peripheral Nerves / enzymology*
  • Peripheral Nerves / pathology
  • Schwann Cells / enzymology
  • Schwann Cells / pathology
  • rho GTP-Binding Proteins / analysis
  • rho GTP-Binding Proteins / genetics*


  • FGD4 protein, human
  • Microfilament Proteins
  • rho GTP-Binding Proteins

Associated data

  • RefSeq/NM_139232
  • RefSeq/NM_139241