Send to

Choose Destination
BMJ Case Rep. 2009;2009. pii: bcr06.2009.1999. doi: 10.1136/bcr.06.2009.1999. Epub 2009 Jul 2.

ARHGEF9 disruption in a female patient is associated with X linked mental retardation and sensory hyperarousal.

Author information

Department of Neurology, University of California, San Francisco, California, USA.


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.

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center