Source:http://linkedlifedata.com/resource/pubmed/id/21441247
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
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| pubmed:dateCreated |
2011-5-23
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| pubmed:abstractText |
Several genes predisposing to autism spectrum disorders (ASDs) with or without epilepsy have been identified, many of which are implicated in synaptic function. Here we report a Q555X mutation in synapsin 1 (SYN1), an X-linked gene encoding for a neuron-specific phosphoprotein implicated in the regulation of neurotransmitter release and synaptogenesis. This nonsense mutation was found in all affected individuals from a large French-Canadian family segregating epilepsy and ASDs. Additional mutations in SYN1 (A51G, A550T and T567A) were found in 1.0 and 3.5% of French-Canadian individuals with autism and epilepsy, respectively. The majority of these SYN1 mutations were clustered in the proline-rich D-domain which is substrate of multiple protein kinases. When expressed in synapsin I (SynI) knockout (KO) neurons, all the D-domain mutants failed in rescuing the impairment in the size and trafficking of synaptic vesicle pools, whereas the wild-type human SynI fully reverted the KO phenotype. Moreover, the nonsense Q555X mutation had a dramatic impact on phosphorylation by MAPK/Erk and neurite outgrowth, whereas the missense A550T and T567A mutants displayed impaired targeting to nerve terminals. These results demonstrate that SYN1 is a novel predisposing gene to ASDs, in addition to epilepsy, and strengthen the hypothesis that a disturbance of synaptic homeostasis underlies the pathogenesis of both diseases.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Jun
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| pubmed:issn |
1460-2083
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| pubmed:author |
pubmed-author:BaldelliPietroP,
pubmed-author:BenfenatiFabioF,
pubmed-author:CongiaSoniaS,
pubmed-author:CorradiAnnaA,
pubmed-author:CossettePatrickP,
pubmed-author:DefranchiEnricoE,
pubmed-author:FaddaManuelaM,
pubmed-author:FassioAnnaA,
pubmed-author:GauthierJulieJ,
pubmed-author:Khoa NguyenDangD,
pubmed-author:LapointeLineL,
pubmed-author:MelocheCarolineC,
pubmed-author:MessaMirkoM,
pubmed-author:MottronLaurentL,
pubmed-author:OnofriFrancoF,
pubmed-author:PatryLysanneL,
pubmed-author:PitonAmelieA,
pubmed-author:PozziDavideD,
pubmed-author:RouleauGuy AGA,
pubmed-author:St-OngeJudithJ,
pubmed-author:ValtortaFlaviaF
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| pubmed:issnType |
Electronic
|
| pubmed:day |
15
|
| pubmed:volume |
20
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
2297-307
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| pubmed:meshHeading |
pubmed-meshheading:21441247-Amino Acid Sequence,
pubmed-meshheading:21441247-Animals,
pubmed-meshheading:21441247-Autistic Disorder,
pubmed-meshheading:21441247-Base Sequence,
pubmed-meshheading:21441247-COS Cells,
pubmed-meshheading:21441247-Cercopithecus aethiops,
pubmed-meshheading:21441247-Codon, Nonsense,
pubmed-meshheading:21441247-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:21441247-Epilepsies, Partial,
pubmed-meshheading:21441247-Gene Knockout Techniques,
pubmed-meshheading:21441247-Humans,
pubmed-meshheading:21441247-Immunoblotting,
pubmed-meshheading:21441247-Lod Score,
pubmed-meshheading:21441247-Mitogen-Activated Protein Kinases,
pubmed-meshheading:21441247-Molecular Sequence Data,
pubmed-meshheading:21441247-Neurons,
pubmed-meshheading:21441247-Pedigree,
pubmed-meshheading:21441247-Phosphorylation,
pubmed-meshheading:21441247-Quebec,
pubmed-meshheading:21441247-Sequence Analysis, DNA,
pubmed-meshheading:21441247-Synapses,
pubmed-meshheading:21441247-Synapsins
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| pubmed:year |
2011
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| pubmed:articleTitle |
SYN1 loss-of-function mutations in autism and partial epilepsy cause impaired synaptic function.
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| pubmed:affiliation |
Department of Experimental Medicine, National Institute of Neuroscience, University of Genova, Viale Benedetto XV 3, 16132 Genova, Italy.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|