title: PAK3 mutation in nonsyndromic X-linked mental retardation.
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.
authors.affiliation: Division of Neurogenetics, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Allen
authors.forename: J G
authors.initials: JG
authors.lastname: Gleeson
authors.forename: S
authors.initials: S
authors.lastname: Bagrodia
authors.forename: M W
authors.initials: MW
authors.lastname: Partington
authors.forename: J C
authors.initials: JC
authors.lastname: MacMillan
authors.forename: R A
authors.initials: RA
authors.lastname: Cerione
authors.forename: J C
authors.initials: JC
authors.lastname: Mulley
authors.forename: C A
authors.initials: CA
authors.lastname: Walsh
mesh_terms: D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D019556:COS Cells; D003001:Cloning, Molecular; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014960:X Chromosome; D054462:p21-Activated Kinases
chemical_list: D011994:Recombinant Proteins; C515911:PAK3 protein, human; C515912:Pak3 protein, mouse; C515913:Pak3 protein, rat; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases