Autism-associated SHANK3 haploinsufficiency causes Ih channelopathy in human neurons
نویسندگان
چکیده
منابع مشابه
Autism-Associated Insertion Mutation (InsG) of Shank3 Exon 21 Causes Impaired Synaptic Transmission and Behavioral Deficits.
SHANK3 (also known as PROSAP2) is a postsynaptic scaffolding protein at excitatory synapses in which mutations and deletions have been implicated in patients with idiopathic autism, Phelan-McDermid (aka 22q13 microdeletion) syndrome, and other neuropsychiatric disorders. In this study, we have created a novel mouse model of human autism caused by the insertion of a single guanine nucleotide int...
متن کاملHaploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication
BACKGROUND SHANK3 is a protein in the core of the postsynaptic density (PSD) and has a critical role in recruiting many key functional elements to the PSD and to the synapse, including components of α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionic acid (AMPA), metabotropic glutamate (mGlu) and N-methyl-D-aspartic acid (NMDA) glutamate receptors, as well as cytoskeletal elements. Loss of a func...
متن کاملHuman Pluripotent Stem Cell-derived Cortical Neurons for High Throughput Medication Screening in Autism: A Proof of Concept Study in SHANK3 Haploinsufficiency Syndrome
Autism spectrum disorders affect millions of individuals worldwide, but their heterogeneity complicates therapeutic intervention that is essentially symptomatic. A versatile yet relevant model to rationally screen among hundreds of therapeutic options would help improving clinical practice. Here we investigated whether neurons differentiated from pluripotent stem cells can provide such a tool u...
متن کاملSHANK3 haploinsufficiency: a “common” but underdiagnosed highly penetrant monogenic cause of autism spectrum disorders
Autism spectrum disorders (ASD) are etiologically heterogeneous, with hundreds of rare, highly penetrant mutations and genomic imbalances involved, each contributing to a very small fraction of cases. In this issue of Molecular Autism, Soorya and colleagues evaluated 32 patients with Phelan-McDermid syndrome, caused by either deletion of 22q13.33 or SHANK3 mutations, using gold-standard diagnos...
متن کاملSHANK3, the synapse, and autism.
Autism spectrum disorders present a paradox of great heterogeneity and great specificity. Well over 100 genetic disorders yield an autism phenotype,1 most through specific but distinct mechanisms, and many of which affect the synapse. SHANK3 (SH3 and multiple ankyrin repeat domains 3) is known to be disrupted in the 22q13 deletion syndrome (Phelan–McDermid syndrome), and variants of SHANK3 have...
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ژورنال
عنوان ژورنال: Science
سال: 2016
ISSN: 0036-8075,1095-9203
DOI: 10.1126/science.aaf2669