Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Genetics & Heredity, Clinical Neurology, Neurosciences & Neurology, Synapse-associated protein 102 (SAP102), X-linked mental retardation (XLMR), Disc-large homolog 3 (DLG3), Methyl-D-aspartate receptor (NMDAR), Membrane-associated guanylate kinase protein (MAGUK), NMDA RECEPTOR, PLASTICITY, TRAFFICKING, Child, Child, Preschool, DNA Mutational Analysis, Exons, Female, Humans, Male, Mental Retardation, X-Linked, Middle Aged, Mutation, Nuclear Proteins, Pedigree, Synapses, Transcription Factors, 0604 Genetics, 1109 Neurosciences, 1702 Cognitive Sciences, Neurology & Neurosurgery, 3105 Genetics, 3202 Clinical sciences, 3209 Neurosciences

Abstract:

We have identified a novel splice site mutation (IVS6-1G > A) in the disc-large homolog 3 (DLG3) gene, encoding the synapse-associated protein 102 (SAP102) in one out of 300 families with moderate to severe non-syndromic mental retardation. SAP102 is a member of the neuronal membrane-associated guanylate kinase protein subfamily comprising SAP97, postsynaptic density (PSD)95, and PSD93, which interacts with methyl-D: -aspartate receptor and associated protein complexes at the postsynaptic density of excitatory synapses. DLG3 is the first mental retardation gene directly linked to glutamate receptor signalling and trafficking, increasingly recognised as a central mechanism in the regulation of synaptic formation and plasticity in brain and cognitive development.