Abstract：
:Although de novo missense mutations have been predicted to account for more cases of autism than gene-truncating mutations, most research has focused on the latter. We identified the properties of de novo missense mutations in patients with neurodevelopmental disorders (NDDs) and highlight 35 genes with excess missense mutations. Additionally, 40 amino acid sites were recurrently mutated in 36 genes, and targeted sequencing of 20 sites in 17,688 patients with NDD identified 21 new patients with identical missense mutations. One recurrent site substitution (p.A636T) occurs in a glutamate receptor subunit, GRIA1. This same amino acid substitution in the homologous but distinct mouse glutamate receptor subunit Grid2 is associated with Lurcher ataxia. Phenotypic follow-up in five individuals with GRIA1 mutations shows evidence of specific learning disabilities and autism. Overall, we find significant clustering of de novo mutations in 200 genes, highlighting specific functional domains and synaptic candidate genes important in NDD pathology.
journal_name
Nat Neuroscijournal_title
Nature neuroscienceauthors
Geisheker MR,Heymann G,Wang T,Coe BP,Turner TN,Stessman HAF,Hoekzema K,Kvarnung M,Shaw M,Friend K,Liebelt J,Barnett C,Thompson EM,Haan E,Guo H,Anderlid BM,Nordgren A,Lindstrand A,Vandeweyer G,Alberti A,Avola E,Vdoi
10.1038/nn.4589subject
Has Abstractpub_date
2017-08-01 00:00:00pages
1043-1051issue
8eissn
1097-6256issn
1546-1726pii
nn.4589journal_volume
20pub_type
杂志文章abstract：:Leptin regulates energy balance. However, knowledge of the critical intracellular transducers of leptin signaling remains incomplete. We found that Rho-kinase 1 (ROCK1) regulates leptin action on body weight homeostasis by activating JAK2, an initial trigger of leptin receptor signaling. Leptin promoted the physical i...
journal_title：Nature neuroscience
pub_type： 杂志文章
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abstract：:The cortical nucleus LMAN (lateral magnocellular nucleus of the anterior nidopallium) provides the output of a basal ganglia pathway that is necessary for vocal learning in juvenile songbirds. The shell subregion of LMAN (LMAN(shell)) gives rise to recurrent loops that may subserve specific learning-related functions....
journal_title：Nature neuroscience
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更新日期：2010-02-01 00:00:00
abstract：:Cocaine is a widely abused substance with psychostimulant effects that are attributed to inhibition of the dopamine transporter (DAT). We present molecular models for DAT binding of cocaine and cocaine analogs constructed from the high-resolution structure of the bacterial transporter homolog LeuT. Our models suggest ...
journal_title：Nature neuroscience
pub_type： 杂志文章
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更新日期：2008-07-01 00:00:00
abstract：:Here we report that synaptic and extrasynaptic NMDA (N-methyl-D-aspartate) receptors have opposite effects on CREB (cAMP response element binding protein) function, gene regulation and neuron survival. Calcium entry through synaptic NMDA receptors induced CREB activity and brain-derived neurotrophic factor (BDNF) gene...
journal_title：Nature neuroscience
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journal_title：Nature neuroscience
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journal_title：Nature neuroscience
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journal_title：Nature neuroscience
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更新日期：2018-04-01 00:00:00
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journal_title：Nature neuroscience
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更新日期：2016-11-01 00:00:00
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journal_title：Nature neuroscience
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更新日期：2015-11-01 00:00:00
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更新日期：2013-04-01 00:00:00
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更新日期：2005-05-01 00:00:00
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更新日期：2017-02-01 00:00:00
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更新日期：2017-12-01 00:00:00
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journal_title：Nature neuroscience
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