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|dc.identifier.citation||American Journal of Human Genetics, 2004; 75(2):318-324||en|
|dc.description.abstract||We have identified truncating mutations in the human DLG3 (neuroendocrine dlg) gene in 4 of 329 families with moderate to severe X-linked mental retardation. DLG3 encodes synapse-associated protein 102 (SAP102), a member of the membrane-associated guanylate kinase protein family. Neuronal SAP102 is expressed during early brain development and is localized to the postsynaptic density of excitatory synapses. It is composed of three amino-terminal PDZ domains, an src homology domain, and a carboxyl-terminal guanylate kinase domain. The PDZ domains interact directly with the NR2 subunits of the NMDA glutamate receptor and with other proteins responsible for NMDA receptor localization, immobilization, and signaling. The mutations identified in this study all introduce premature stop codons within or before the third PDZ domain, and it is likely that this impairs the ability of SAP102 to interact with the NMDA receptor and/or other proteins involved in downstream NMDA receptor signaling pathways. NMDA receptors have been implicated in the induction of certain forms of synaptic plasticity, such as long-term potentiation and long-term depression, and these changes in synaptic efficacy have been proposed as neural mechanisms underlying memory and learning. The disruption of NMDA receptor targeting or signaling, as a result of the loss of SAP102, may lead to altered synaptic plasticity and may explain the intellectual impairment observed in individuals with DLG3 mutations.||en|
|dc.description.statementofresponsibility||Patrick Tarpey, Josep Parnau, Matthew Blow, Hayley Woffendin, Graham Bignell, Charles Cox, James Cox, Helen Davies, Sarah Edkins, Simon Holden, Angelique Korny, Uma Mallya, Jenny Moon, Sarah O’Meara, Adrian Parker, Philip Stephens, Claire Stevens, Jon Teague, Andrew Donnelly, Marie Mangelsdorf, John Mulley,Michael Partington,Gillian Turner, Roger Stevenson, Charles Schwartz, Ian Young, Douglas Easton, Martin Bobrow, P. Andrew Futreal, Michael R. Stratton, Jozef Gecz, Richard Wooster and F. Lucy Raymond||en|
|dc.publisher||Univ Chicago Press||en|
|dc.rights||Copyright © 2004 The American Society of Human Genetics Published by Elsevier Inc.||en|
|dc.subject||Chromosomes, Human, X; Humans; Mental Retardation, X-Linked; Nuclear Proteins; Transcription Factors; Pedigree; Sequence Deletion; Base Sequence; Molecular Sequence Data; Female; Male||en|
|dc.title||Mutations in the DLG3 gene cause nonsyndromic X-linked mental retardation||en|
|dc.identifier.orcid||Gecz, J. [0000-0002-7884-6861]||en|
|Appears in Collections:||Paediatrics publications|
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