PAK3 Mutation in Nonsyndromic X-linked Mental Retardation

Nat Genet. 1998 Sep;20(1):25-30. doi: 10.1038/1675.

Abstract

Nonsyndromic X-linked mental retardation (MRX) syndromes are clinically homogeneous but genetically heterogeneous disorders, whose genetic bases are largely unknown. Affected individuals in a multiplex pedigree with MRX (MRX30), previously mapped to Xq22, show a point mutation in the PAK3 (p21-activated kinase) gene, which encodes a serine-threonine kinase. PAK proteins are crucial effectors linking Rho GTPases to cytoskeletal reorganization and to nuclear signalling. The mutation produces premature termination, disrupting kinase function. MRI analysis showed no gross defects in brain development. Immunofluorescence analysis showed that PAK3 protein is highly expressed in postmitotic neurons of the developing and postnatal cerebral cortex and hippocampus. Signal transduction through Rho GTPases and PAK3 may be critical for human cognitive function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Brain / metabolism*
  • COS Cells
  • Cloning, Molecular
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Intellectual Disability / genetics*
  • Male
  • Mice
  • Molecular Sequence Data
  • Mutation*
  • Pedigree
  • Protein-Serine-Threonine Kinases / genetics*
  • Protein-Serine-Threonine Kinases / metabolism
  • Rats
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Analysis, DNA
  • X Chromosome*
  • p21-Activated Kinases

Substances

  • Recombinant Proteins
  • PAK3 protein, human
  • Pak3 protein, mouse
  • Pak3 protein, rat
  • Protein-Serine-Threonine Kinases
  • p21-Activated Kinases

Associated data

  • GENBANK/AF068864
  • GENBANK/U24152
  • GENBANK/U24153
  • GENBANK/U25975
  • GENBANK/U33314
  • GENBANK/V39738