A novel mutation in the DLG3 gene encoding the synapse-associated protein 102 (SAP102) causes non-syndromic mental retardation.
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.
Zanni
Ginevra
G
Institut Cochin, Université Paris Descartes, INSERM, CNRS UMR 8104, CHU Cochin, Paris, France. ginevra.zanni@opbg.net
van Esch
Hilde
H
Bensalem
Anissa
A
Saillour
Yoann
Y
Poirier
Karine
K
Castelnau
Laetitia
L
Ropers
Hans Hilger
HH
de Brouwer
Arjan P M
AP
Laumonnier
Fréderic
F
Fryns
Jean-Pierre
JP
Chelly
Jamel
J
D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics* / Q000503:physiopathology; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D013569:Synapses / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
C116869:DLG3 protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors