|
Autism Spectrum Disorders
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Developmental loss of ASD-associated genes Shank3 or Mecp2 in peripheral mechanosensory neurons leads to region-specific brain abnormalities, revealing links between developmental somatosensory over-reactivity and the genesis of aberrant behaviors.
|
31398341 |
2019 |
|
Autism Spectrum Disorders
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Rare mutations in SHANK3 have been associated with idiopathic ASDs, non-syndromic intellectual disability, and schizophrenia.
|
24132240 |
2013 |
|
Autism Spectrum Disorders
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Our data support that recurrent genomic rearrangements at 22q13.3 are part of the genetic landscape of ASD in our patients and changes in SHANK3 dosage are associated with neurodevelopmental disorders.
|
27846046 |
2017 |
|
Autism Spectrum Disorders
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Previous studies have shown that Autism spectrum disorder is a result of mutations of the main SHANK3 isoforms, which may be due to deficit in excitatory synaptic transmission and plasticity.
|
27592227 |
2017 |
|
Autism Spectrum Disorders
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Given the zinc sensitivity of young neurons and its dependence on Shank2 and Shank3, genetic mutations and/or environmental insults during early development could impair synaptic maturation and circuit formation that underlie ASD etiology.
|
30524232 |
2018 |
|
Autism Spectrum Disorders
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
While SHANK3 variants are present in any ASD subtype, the SNP rs76224556 appears to be significantly associated with PDD-NOS cases.
|
22892527 |
2013 |
|
Autism Spectrum Disorders
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Therefore, in CA3 pyramidal neurons of Shank3-mutant mice, glutamatergic but not GABAergic activity is affected at early developmental stages, hence reflecting the heterogeneity of mechanisms underlying the pathogenesis of ASD.
|
31354805 |
2019 |
|
Autism Spectrum Disorders
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
We identified a mutation in SHANK3 that underscores its relevance in Autism Spectrum Disorder.
|
25646853 |
2015 |
|
Autism Spectrum Disorders
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
The E183V mutation also reduces CaMKIIα binding to established ASD-linked proteins, such as Shank3 and subunits of l-type calcium channels and NMDA receptors, and increases CaMKIIα turnover in intact cells.
|
28130356 |
2017 |
|
Autism Spectrum Disorders
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
These results, obtained through the analysis of de novo SHANK3 mutations in the patients' genomic background, provide further support for the presence of synaptic abnormalities in a subset of patients with ASD.
|
30643170 |
2019 |
|
Autism Spectrum Disorders
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Intriguingly, all ASD Shank3 mutations impaired mGluR-dependent LTD without altering NMDAR-dependent LTD. Our data show that the specific perturbation in mGluR-dependent synaptic plasticity occurs in neurons expressing ASD-associated Shank3 mutations, which may underpin synaptic dysfunction and subsequent behavioral deficits in ASD.
|
30868621 |
2019 |
|
Autism Spectrum Disorders
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
We generated induced pluripotent stem cells (iPSCs) from control individuals and from human donors with ASD carrying microdeletions of SHANK3.
|
28948968 |
2018 |
|
Autism Spectrum Disorders
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
De novo mutations (DNMs) of SHANK3 were subsequently identified in patients with several neurodevelopmental disorders, including autism spectrum disorders (ASDs), schizophrenia (SCZ), a Rett syndrome-like phenotype, and intellectual disability (ID).
|
30537371 |
2018 |
|
Autism Spectrum Disorders
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
In contrast, the frequency and the penetrance of SHANK3 mutations in individuals with ASD and intellectual disability-more than 1 in 50-warrant its consideration for mutation screening in clinical practice.
|
25188300 |
2014 |
|
Autism Spectrum Disorders
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Male mice with a deletion of the PDZ domain of Shank3 (Shank3B KO) were previously shown to display ASD-like behavioral phenotypes with reported self-injurious repetitive grooming and aberrant social interactions.
|
30134148 |
2019 |
|
Autism Spectrum Disorders
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Environmental enrichment has minimal effects on behavior in the Shank3 complete knockout model of autism spectrum disorder.
|
30317697 |
2018 |
|
Autism Spectrum Disorders
|
0.700 |
Biomarker
|
disease |
BEFREE |
Recent studies have strongly implicated postsynaptic scaffolding proteins such as SAPAP3 or Shank3 in the pathogenesis of various mood disorders, including autism spectrum disorder, bipolar disorder (BD), and obsessive-compulsive disorders.
|
27530683 |
2016 |
|
Autism Spectrum Disorders
|
0.700 |
Biomarker
|
disease |
BEFREE |
SHANK3 has been described in the Phelan-McDermid syndrome (PMS), but also in autism spectrum disorders (ASD) and schizophrenia associated to moderate to severe intellectual disability (ID) and poor language.
|
24124131 |
2014 |
|
Autism Spectrum Disorders
|
0.700 |
Biomarker
|
disease |
BEFREE |
To further analyse the involvement of SHANK3 in ASD, we screened the International Molecular Genetic Study of Autism Consortium (IMGSAC) multiplex family sample, 330 families, for SNP association and copy number variants (CNVs) in SHANK3.
|
19384346 |
2009 |
|
Autism Spectrum Disorders
|
0.700 |
Biomarker
|
disease |
BEFREE |
Studies of genomic copy number variants (CNVs) have identified genes associated with autism spectrum disorder (ASD) and intellectual disability (ID) such as NRXN1, SHANK2, SHANK3 and PTCHD1.
|
25131214 |
2015 |
|
Autism Spectrum Disorders
|
0.700 |
Biomarker
|
disease |
BEFREE |
Among the most promising candidate genes for ASD is the SHANK gene family, including SHANK1, SHANK2 (ProSAP1), and SHANK3 (ProSAP2).
|
24726578 |
2014 |
|
Autism Spectrum Disorders
|
0.700 |
Biomarker
|
disease |
BEFREE |
Here we used two highly trusted ASD mouse models (male Shank3-deficient [Shank3<sup>+/ΔC</sup> ] mice modeling the monogenic etiology of ASD, and inbred BTBR mice [both male and female] modeling the idiopathic and highly polygenic pathology for ASD) to evaluate the level of motivation to engage in a social interaction.
|
31602784 |
2020 |
|
Autism Spectrum Disorders
|
0.700 |
Biomarker
|
disease |
BEFREE |
We found that gene expression of mGluR5 was significantly decreased in ASD versus controls (p=0.018) as well as downstream elements SHANK3 (p=0.005) and PLCB1 (p=0.009) but that the pro-inflammatory marker NOS2 was increased (p=0.047).
|
26052099 |
2015 |
|
Autism Spectrum Disorders
|
0.700 |
Biomarker
|
disease |
CTD_human |
Notwithstanding complexities, our results further implicate the SHANK3-NLGN4-NRXN1 postsynaptic density genes and also identify novel loci at DPP6-DPP10-PCDH9 (synapse complex), ANKRD11, DPYD, PTCHD1, 15q24, among others, for a role in ASD susceptibility.
|
18252227 |
2008 |
|
Autism Spectrum Disorders
|
0.700 |
Biomarker
|
disease |
BEFREE |
SHANK3 is one of the genes that underpins the synaptic hypothesis for ASD.
|
24218108 |
2014 |