title: PAK3 related mental disability: further characterization of the phenotype.
abstract: We report clinical, neuropsychological and molecular findings in affected males and carrier females in the fourth reported family with mental retardation caused by mutation in the PAK3 gene (Xq22.3-q23), W446S. In contrast to previous reports, carrier females manifested learning problems and mild mental disability. Skewed X-inactivation was observed here for the first time in carriers of PAK3 mutation. Neuropsychological tests in affected males and carrier females suggested a common neuropsychological profile of impaired spatial cognitive abilities and defects in attentional and executive functions. The five affected males examined herein had a proportionally small head size or microcephaly, large ears, oral motor hypotonia with drooling and inarticulate speech and short attention span, anxiety, restlessness, and aggression. Brain imaging showed signs of chronic non-progressive hydrocephalus in one patient who manifested psychosis and fluctuant gait deterioration, while two other patients showed no abnormalities. EEG recordings were available from four affected males and one carrier female, and all showed similar posterior slow wave activity without epileptic discharges. Only one affected male in the family suffered from epilepsy. When comparing the affected males in this family and the three previously reported families with mental retardation due to a PAK3 mutation, similarities in their characteristics were small head size or microcephaly, large ears, speech defects, behavioral abnormalities, and psychiatric disease.
authors.affiliation: Department of Medical Genetics, Family Federation of Finland, Helsinki, Finland. maarit.peippo@vaestoliitto.fi
authors.forename: Maarit
authors.initials: M
authors.lastname: Peippo
authors.forename: Anne M
authors.initials: AM
authors.lastname: Koivisto
authors.forename: Teppo
authors.initials: T
authors.lastname: Särkämö
authors.forename: Marjatta
authors.initials: M
authors.lastname: Sipponen
authors.forename: Harriet
authors.initials: H
authors.lastname: von Koskull
authors.forename: Tero
authors.initials: T
authors.lastname: Ylisaukko-oja
authors.forename: Karola
authors.initials: K
authors.lastname: Rehnström
authors.forename: Guy
authors.initials: G
authors.lastname: Froyen
authors.forename: Jaakko
authors.initials: J
authors.lastname: Ignatius
authors.forename: Irma
authors.initials: I
authors.lastname: Järvelä
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009483:Neuropsychological Tests; D010375:Pedigree; D010641:Phenotype; D016415:Sequence Alignment; D054462:p21-Activated Kinases / Q000235:genetics*
chemical_list: C515911:PAK3 protein, human; D054462:p21-Activated Kinases