ARHGEF9 disruption in a female patient is associated with X linked mental retardation and sensory hyperarousal
- 1Department of Neurology, University of California, San Francisco, California, USA
- 2Greenwood Genetic Center, Greenwood, South Carolina, USA
- 3Joint Genome Institute, Lawrence Berkeley National Laboratories, Berkeley, California, USA
- 4Cardiovascular Research Institute, University of California, San Francisco, California, USA
- 5Department of Pathology, Children’s Hospital and Research Center at Oakland, Oakland, California, USA
- 6Pediatric Clinical Research Center, University of California, San Francisco, California, USA
- Elliott H Sherr, sherre{at}neuropeds.ucsf.edu
- Published 2 July 2009
Summary
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.
Footnotes
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Competing interests: none.
