Convergence of Hippocampal Pathophysiology in Syngap+/- and Fmr1-/y Mice.
Edinburgh, United Kingdom. In J Neurosci, 11 Dec 2015
Super-resolution microscopy reveals that Syngap(+/-) and Fmr1(-/y) mice show nanoscale alterations in dendritic spine morphology that predict an increase in biochemical compartmentalization. Finally, increased basal protein synthesis is rescued by negative regulators of the mGlu subtype 5 receptor and the Ras-ERK1/2 pathway, indicating that therapeutic interventions for fragile X syndrome may benefit patients with SYNGAP1 haploinsufficiency.
Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing.
Illkirch-Graffenstaden, France. In J Med Genet, 2014
RESULTS: We identified 26 causative mutations: 16 in X-linked genes (ATRX, CUL4B, DMD, FMR1, HCFC1, IL1RAPL1, IQSEC2, KDM5C, MAOA, MECP2, SLC9A6, SLC16A2, PHF8) and 10 de novo in autosomal-dominant genes (DYRK1A, GRIN1, MED13L, TCF4, RAI1, SHANK3, SLC2A1, SYNGAP1).
SynGAP isoforms exert opposing effects on synaptic strength.
Edinburgh, United Kingdom. In Nat Commun, 2011
Overexpression of SynGAP alpha1 versus alpha2 C-termini-containing proteins in hippocampal neurons has opposing effects on synaptic strength, decreasing and increasing miniature excitatory synaptic currents amplitude/frequency, respectively.
De novo autosomal dominant mutation in SYNGAP1.
Chicago, United States. In Autism Res, 2011
SYNGAP1 is a brain-specific protein that interacts with key components of the proteins involved in experience-dependent changes in glutamate synapses involved in learning.