A Balanced Chromosomal Translocation Disrupting ARHGEF9 Is Associated With Epilepsy, Anxiety, Aggression, and Mental Retardation

作者：Kalscheuer Vera M; Musante Luciana; Fang Cheng; Hoffmann Kirsten; Fuchs Celine; Carta Eloisa; Deas Emma; Venkateswarlu Kanamarlapudi; Menzel Corinna; Ullmann Reinhard; Tommerup Niels; Dalpra Leda; Tzschach Andreas; Selicorni Angelo; Luescher Bernhard; Ropers Hans Hilger; Harvey Kirsten; Harvey Robert J^*

来源：Human Mutation, 2009, 30(1): 61-68.

DOI：10.1002/humu.20814

• GABA(A) receptors
• glycine receptors
• collybistin
• ARHGEF9
• gephyrin
• clustering
• anxiety
• epilepsy
• mental retardation
• aggression

Clustering of inhibitory gamma-aminobutyric acid(A) (GABA(A)) and glycine receptors at synapses is thought to involve key interactions between the receptors, a "scaffolding" protein known as gephyrin and the RhoGEF collybistin. We report the identification of a balanced chromosomal translocation in a female patient presenting with a disturbed sleep wake cycle, late-onset epileptic seizures, increased anxiety, aggressive behavior, and mental retardation, but not hyperekplexia. Fine mapping of the breakpoint indicates disruption of the collybistin gene (ARHGEF9) on chromosome Xq11, while the other breakpoint lies in a region of 18q11 that lacks any known or predicted genes. We show that defective collybistin transcripts are synthesized and exons 7-10 are replaced by cryptic exons from chromosomes X and 18. These mRNAs no longer encode the pleckstrin homology (PH) domain of collybistin, which we now

• 出版日期2009-1