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dc.contributor.author
Salpietro, Vincenzo
dc.contributor.author
Malintan, Nancy T.
dc.contributor.author
Llano Rivas, Isabel
dc.contributor.author
Spaeth, Christine G.
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Efthymiou, Stephanie
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Striano, Pasquale
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Vandrovcova, Jana
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Cutrupi, Maria Concetta
dc.contributor.author
Chimenz, Roberto
dc.contributor.author
David, Emanuele
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Di Rosa, Gabriella
dc.contributor.author
Marce Grau, Anna
dc.contributor.author
Raspall Chaure, Miquel
dc.contributor.author
Martin Hernandez, Elena
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Zara, Federico
dc.contributor.author
Minetti, Carlo
dc.contributor.author
Bello, Oscar Daniel
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De Zorzi, Rita
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Fortuna, Sara
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Dauber, Andrew
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Alkhawaja, Mariam
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Sultan, Tipu
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Mankad, Kshitij
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Vitobello, Antonio
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Thomas, Quentin
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Tran Mau Them, Frederic
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Faivre, Laurence
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Martinez Azorin, Francisco
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Prada, Carlos E.
dc.contributor.author
Macaya, Alfons
dc.date.available
2022-06-21T10:48:26Z
dc.date.issued
2019-03
dc.identifier.citation
Salpietro, Vincenzo; Malintan, Nancy T.; Llano Rivas, Isabel; Spaeth, Christine G.; Efthymiou, Stephanie; et al.; Mutations in the Neuronal Vesicular SNARE VAMP2 Affect Synaptic Membrane Fusion and Impair Human Neurodevelopment; Cell Press; American Journal Of Human Genetics; 104; 4; 3-2019; 721-730
dc.identifier.issn
0002-9297
dc.identifier.uri
http://hdl.handle.net/11336/160046
dc.description.abstract
VAMP2 encodes the vesicular SNARE protein VAMP2 (also called synaptobrevin-2). Together with its partners syntaxin-1A and synaptosomal-associated protein 25 (SNAP25), VAMP2 mediates fusion of synaptic vesicles to release neurotransmitters. VAMP2 is essential for vesicular exocytosis and activity-dependent neurotransmitter release. Here, we report five heterozygous de novo mutations in VAMP2 in unrelated individuals presenting with a neurodevelopmental disorder characterized by axial hypotonia (which had been present since birth), intellectual disability, and autistic features. In total, we identified two single-amino-acid deletions and three non-synonymous variants affecting conserved residues within the C terminus of the VAMP2 SNARE motif. Affected individuals carrying de novo non-synonymous variants involving the C-terminal region presented a more severe phenotype with additional neurological features, including central visual impairment, hyperkinetic movement disorder, and epilepsy or electroencephalography abnormalities. Reconstituted fusion involving a lipid-mixing assay indicated impairment in vesicle fusion as one of the possible associated disease mechanisms. The genetic synaptopathy caused by VAMP2 de novo mutations highlights the key roles of this gene in human brain development and function.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Cell Press
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
AUTISM
dc.subject
EPILEPSY
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MOVEMENT DISORDERS
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NEURODEVELOPMENTAL DISORDERS
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NEURONAL EXOCYTOSIS
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SNARE
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SYNAPTOBREVIN
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SYNAPTOPATHY
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VAMP2
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VESICLE FUSION
dc.subject.classification
Neurociencias
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Mutations in the Neuronal Vesicular SNARE VAMP2 Affect Synaptic Membrane Fusion and Impair Human Neurodevelopment
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2022-06-16T14:06:51Z
dc.journal.volume
104
dc.journal.number
4
dc.journal.pagination
721-730
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Salpietro, Vincenzo. Università degli Studi di Genova; Italia. University College London; Estados Unidos
dc.description.fil
Fil: Malintan, Nancy T.. Università degli Studi di Genova; Italia
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Fil: Llano Rivas, Isabel. Hospital Universitario Cruces; España
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Fil: Spaeth, Christine G.. University of Cincinnati; Estados Unidos
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Fil: Efthymiou, Stephanie. University College London; Estados Unidos
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Fil: Striano, Pasquale. Istituto Giannina Gaslini; Italia. University of Genoa; Italia
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Fil: Vandrovcova, Jana. University College London; Estados Unidos
dc.description.fil
Fil: Cutrupi, Maria Concetta. University of Messina; Italia
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Fil: Chimenz, Roberto. University of Messina; Italia
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Fil: David, Emanuele. Papardo University Hospital; Italia
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Fil: Di Rosa, Gabriella. University of Messina; Italia
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Fil: Marce Grau, Anna. University Hospital Vall d’Hebron; España
dc.description.fil
Fil: Raspall Chaure, Miquel. University Hospital Vall d’Hebron; España
dc.description.fil
Fil: Martin Hernandez, Elena. Hospital 12 de Octubre; España
dc.description.fil
Fil: Zara, Federico. Istituto Giannina Gaslini; Italia
dc.description.fil
Fil: Minetti, Carlo. Istituto Giannina Gaslini; Italia
dc.description.fil
Fil: Bello, Oscar Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
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Fil: De Zorzi, Rita. Università degli Studi di Trieste; Italia
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Fil: Fortuna, Sara. Università degli Studi di Trieste; Italia
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Fil: Dauber, Andrew. Cincinnati Children's Hospital Medical Center; Estados Unidos
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Fil: Alkhawaja, Mariam. No especifíca;
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Fil: Sultan, Tipu. Institute of Child Health and The Children’s Hospital Lahore; Pakistán
dc.description.fil
Fil: Mankad, Kshitij. Great Ormond Street Hospital for Children; Reino Unido
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Fil: Vitobello, Antonio. Center Hospitalier Universitaire Dijon Bourgogne; Francia
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Fil: Thomas, Quentin. Center Hospitalier Universitaire Dijon Bourgogne; Francia
dc.description.fil
Fil: Tran Mau Them, Frederic. Center Hospitalier Universitaire Dijon Bourgogne; Francia
dc.description.fil
Fil: Faivre, Laurence. Hospital d’Enfants, Dijon; Francia. Center Hospitalier Universitaire Dijon Bourgogne; Francia
dc.description.fil
Fil: Martinez Azorin, Francisco. No especifíca;
dc.description.fil
Fil: Prada, Carlos E.. University of Cincinnati; Estados Unidos
dc.description.fil
Fil: Macaya, Alfons. University Hospital Vall d’Hebron; España
dc.journal.title
American Journal Of Human Genetics
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0002929719300618
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1016/j.ajhg.2019.02.016
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