Allen, K.Gleeson, J.Bagrodia, S.Partington, M.MacMillan, J.Cerione, R.Mulley, J.Walsh, C.2006-07-052006-07-051998Nature Genetics, 1998; 20(1):25-301061-40361546-1718http://hdl.handle.net/2440/11492Nonsyndromic 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.enBrainCOS CellsX ChromosomeAnimalsHumansMiceRatsRecombinant ProteinsFluorescent Antibody Technique, IndirectCloning, MolecularPedigreeSequence Analysis, DNABase SequenceMutationMolecular Sequence DataFemaleMalep21-Activated KinasesIntellectual DisabilityProtein Serine-Threonine KinasesJournal article0030004273001998210310.1038/16752-s2.0-003171055768279