Rare exonic deletions implicate the synaptic organizer gephyrin (GPHN) in risk for autism, schizophrenia and seizures

Anath C. Lionel, Andrea K. Vaags, Daisuke Sato, Matthew J. Gazzellone, Elyse B. Mitchell, Hong Yang Chen, Gregory Costain, Susan Walker, Gerald Egger, Bhooma Thiruvahindrapuram, Daniele Merico, Aparna Prasad, Evdokia Anagnostou, Eric Fombonne, Lonnie Zwaigenbaum, Wendy Roberts, Peter Szatmari, Bridget A. Fernandez, Lyudmila Georgieva, Linda M. BrzustowiczKatharina Roetzer, Wolfgang Kaschnitz, John B. Vincent, Christian Windpassinger, Christian R. Marshall, Rosario R. Trifiletti, Salman Kirmani, George Kirov, Erwin Petek, Jennelle C. Hodge, Anne S. Bassett, Stephen W. Scherer

Research output: Contribution to journalArticlepeer-review

96 Scopus citations


The GPHN gene codes for gephyrin, a key scaffolding protein in the neuronal postsynaptic membrane, responsible for the clustering and localization of glycine and GABA receptors at inhibitory synapses. Gephyrin has well-established functional links with several synaptic proteins that have been implicated in genetic risk for neurodevelopmental disorders such as autism spectrum disorder (ASD), schizophrenia and epilepsy including the neuroligins (NLGN2, NLGN4), the neurexins (NRXN1, NRXN2, NRXN3) and collybistin (ARHGEF9). Moreover, temporal lobe epilepsy has been linked to abnormally spliced GPHN mRNA lacking exons encoding the G-domain of the gephyrin protein, potentially arising due to cellular stress associated with epileptogenesis such as temperature and alkalosis. Here, we present clinical and genomic characterization of six unrelated subjects, with a range of neurodevelopmental diagnoses including ASD, schizophrenia or seizures, who possess rare de novo or inherited hemizygous microdeletions overlapping exons of GPHN at chromosome 14q23.3. The region of common overlap across the deletions encompasses.

Original languageEnglish (US)
Pages (from-to)2055-2066
Number of pages12
JournalHuman molecular genetics
Issue number10
StatePublished - May 2013

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)


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