title: ARHGEF9 disruption in a female patient is associated with X linked mental retardation and sensory hyperarousal.
abstract: We identified a female patient with mental retardation and sensory hyperarousal. She has a de novo paracentric inversion of one X chromosome with completely skewed inactivation of the normal X chromosome. We aimed to identify whether a single gene or gene region caused her cognitive and behavioural impairment and that of others. Fluorescent in situ hybridisation (FISH) showed that the centromeric breakpoint disrupts a single gene: ARHGEF9 (CDC42 guanine nucleotide exchange factor (GEF) 9). We also found that the levels of the ARHGEF9 transcript from the patient are 10-fold less than those found in control samples. ARHGEF9 encodes a RhoGEF family protein: collybistin (hPEM), which is highly expressed in the brain. Collybistin can regulate actin cytoskeletal dynamics and may also modulate GABAergic and glycinergic neurotransmission through binding of a scaffolding protein, gephyrin, at the synapse. This potential dual role may explain both the mental retardation and hyperarousal observed in our patient.
authors: Department of Neurology, University of California, San Francisco, California, USA.
authors: E J
authors: EJ
authors: Marco
authors: F E
authors: FE
authors: Abidi
authors: J
authors: J
authors: Bristow
authors: W B
authors: WB
authors: Dean
authors: P
authors: P
authors: Cotter
authors: R J
authors: RJ
authors: Jeremy
authors: C E
authors: CE
authors: Schwartz
authors: E H
authors: EH
authors: Sherr