| Titre : |
SHANK Mutations in Intellectual Disability and Autism Spectrum Disorder |
| Type de document : |
Texte imprimé et/ou numérique |
| Auteurs : |
Michael J. SCHMEISSER, Auteur ; Chiara VERPELLI, Auteur |
| Année de publication : |
2016 |
| Importance : |
p.151-160 |
| Langues : |
Anglais (eng) |
| Mots-clés : |
Autism spectrum disorder Intellectual disability Shank1 Shank2 Shank3 Synapse |
| Index. décimale : |
SCI-D SCI-D - Neurosciences |
| Résumé : |
Mutations in the three human SHANK genes, which encode the postsynaptic scaffold proteins SHANK1, SHANK2, and SHANK3, are directly responsible for certain types of intellectual disability (ID) and in general for autism spectrum disorder (ASD). These neuropsychiatric conditions are caused by a generalized dysfunction of the brain, most probably owing to altered formation and plasticity of synaptic connections, thus leading to dysfunctional neuronal communication. Most interestingly, SHANK mutations affect individuals with a different grade of severity: that is, patients with SHANK3 mutations exhibit a strong ID and ASD phenotype, whereas patients with SHANK2 or SHANK1 mutations characteristically exhibit milder phenotypes. To summarize current knowledge about the effects of SHANK mutations on the pathogenesis of ID and ASD, we will discuss the impact of SHANK on synaptic function and highlight genotypic and phenotypic variations among mutations. Whereas the foundation of our knowledge on SHANK function began with in vitro studies, in vivo investigation of Shank mutant mice has further advanced our studies. Functional analysis of rodent Shank family members allows us to understand the role of these proteins better in brain development and in the pathogenesis of ID and ASD with the ultimate aim of identifying novel targets to develop effective therapies. With the recent discovery of human induced pluripotent stem cells, the ability to work on human neurons has opened up, potentially allowing for precise genetic mapping and possibly even personalized therapies to be developed. In this chapter, we will present an overview of SHANK function and SHANK mutations from the perspective of both in vitro and in vivo studies pointing to future directions where research on SHANK will likely go. |
| En ligne : |
http://dx.doi.org/10.1016/B978-0-12-800109-7.00010-8 |
| Permalink : |
https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301 |
SHANK Mutations in Intellectual Disability and Autism Spectrum Disorder [Texte imprimé et/ou numérique] / Michael J. SCHMEISSER, Auteur ; Chiara VERPELLI, Auteur . - 2016 . - p.151-160. Langues : Anglais ( eng)
| Mots-clés : |
Autism spectrum disorder Intellectual disability Shank1 Shank2 Shank3 Synapse |
| Index. décimale : |
SCI-D SCI-D - Neurosciences |
| Résumé : |
Mutations in the three human SHANK genes, which encode the postsynaptic scaffold proteins SHANK1, SHANK2, and SHANK3, are directly responsible for certain types of intellectual disability (ID) and in general for autism spectrum disorder (ASD). These neuropsychiatric conditions are caused by a generalized dysfunction of the brain, most probably owing to altered formation and plasticity of synaptic connections, thus leading to dysfunctional neuronal communication. Most interestingly, SHANK mutations affect individuals with a different grade of severity: that is, patients with SHANK3 mutations exhibit a strong ID and ASD phenotype, whereas patients with SHANK2 or SHANK1 mutations characteristically exhibit milder phenotypes. To summarize current knowledge about the effects of SHANK mutations on the pathogenesis of ID and ASD, we will discuss the impact of SHANK on synaptic function and highlight genotypic and phenotypic variations among mutations. Whereas the foundation of our knowledge on SHANK function began with in vitro studies, in vivo investigation of Shank mutant mice has further advanced our studies. Functional analysis of rodent Shank family members allows us to understand the role of these proteins better in brain development and in the pathogenesis of ID and ASD with the ultimate aim of identifying novel targets to develop effective therapies. With the recent discovery of human induced pluripotent stem cells, the ability to work on human neurons has opened up, potentially allowing for precise genetic mapping and possibly even personalized therapies to be developed. In this chapter, we will present an overview of SHANK function and SHANK mutations from the perspective of both in vitro and in vivo studies pointing to future directions where research on SHANK will likely go. |
| En ligne : |
http://dx.doi.org/10.1016/B978-0-12-800109-7.00010-8 |
| Permalink : |
https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301 |
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SHANK Mutations in Intellectual Disability and Autism Spectrum Disorder
