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SHR Neuro Krebs Kardio Lipid

Lionel, AC; Vaags, AK; Sato, D; Gazzellone, MJ; Mitchell, EB; Chen, HY; Costain, G; Walker, S; Egger, G; Thiruvahindrapuram, B; Merico, D; Prasad, A; Anagnostou, E; Fombonne, E; Zwaigenbaum, L; Roberts, W; Szatmari, P; Fernandez, BA; Georgieva, L; Brzustowicz, LM; Roetzer, K; Kaschnitz, W; Vincent, JB; Windpassinger, C; Marshall, CR; Trifiletti, RR; Kirmani, S; Kirov, G; Petek, E; Hodge, JC; Bassett, AS; Scherer, SW.
Rare exonic deletions implicate the synaptic organizer Gephyrin (GPHN) in risk for autism, schizophrenia and seizures.
Hum Mol Genet. 2013; 22(10):2055-2066 [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Kaschnitz Wolfgang
Petek Erwin
Rötzer Katharina Magdalena
Windpassinger Christian
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Abstract:
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 exons 3-5, corresponding to the G-domain of the gephyrin protein. These findings, together with previous reports of homozygous GPHN mutations in connection with autosomal recessive molybdenum cofactor deficiency, will aid in clinical genetic interpretation of the GPHN mutation spectrum. Our data also add to the accumulating evidence implicating neuronal synaptic gene products as key molecular factors underlying the etiologies of a diverse range of neurodevelopmental conditions.
Find related publications in this database (using NLM MeSH Indexing)
Autistic Disorder -
Base Sequence -
Carrier Proteins - genetics
Cell Adhesion Molecules, Neuronal - genetics
Chromosomes, Human, Pair 14 - genetics
Exons -
Female -
Guanine Nucleotide Exchange Factors - genetics
Humans -
Male -
Membrane Proteins - genetics
Nerve Tissue Proteins - genetics
RNA Splicing - genetics
Receptors, GABA - genetics
Receptors, Glycine - genetics
Rho Guanine Nucleotide Exchange Factors -
Schizophrenia - genetics
Seizures - genetics
Sequence Deletion -
Synaptic Membranes - genetics

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