دورية أكاديمية
Mutations in the Neuronal Vesicular SNARE VAMP2 Affect Synaptic Membrane Fusion and Impair Human Neurodevelopment
| العنوان: | Mutations in the Neuronal Vesicular SNARE VAMP2 Affect Synaptic Membrane Fusion and Impair Human Neurodevelopment |
|---|---|
| المؤلفون: | Salpietro, Vincenzo, Malintan, Nancy T., Llano Rivas, Isabel, Spaeth, Christine G., Efthymiou, Stephanie, Striano, Pasquale, Vandrovcova, Jana, Cutrupi, Maria Concetta, Chimenz, Roberto, David, Emanuele, Di Rosa, Gabriella, Marce Grau, Anna, Raspall Chaure, Miquel, Martin Hernandez, Elena, Zara, Federico, Minetti, Carlo, Bello, Oscar Daniel, De Zorzi, Rita, Fortuna, Sara, Dauber, Andrew, Alkhawaja, Mariam, Sultan, Tipu, Mankad, Kshitij, Vitobello, Antonio, Thomas, Quentin, Tran Mau Them, Frederic, Faivre, Laurence, Martinez Azorin, Francisco, Prada, Carlos E., Macaya, Alfons |
| بيانات النشر: | Cell Press |
| المجموعة: | CONICET Digital (Consejo Nacional de Investigaciones Científicas y Técnicas) |
| مصطلحات موضوعية: | AUTISM, EPILEPSY, MOVEMENT DISORDERS, NEURODEVELOPMENTAL DISORDERS, NEURONAL EXOCYTOSIS, SNARE, SYNAPTOBREVIN, SYNAPTOPATHY, VAMP2, VESICLE FUSION, https://purl.org/becyt/ford/3.1Test, https://purl.org/becyt/ford/3Test |
| الوصف: | 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. ; Fil: Salpietro, Vincenzo. Università degli Studi di Genova; Italia. University College London; Estados Unidos ; Fil: Malintan, Nancy T. Università degli Studi di Genova; Italia ; Fil: Llano Rivas, Isabel. Hospital Universitario Cruces; España ; Fil: Spaeth, Christine G. University of Cincinnati; Estados Unidos ; Fil: Efthymiou, Stephanie. University College London; Estados Unidos ; Fil: Striano, Pasquale. Istituto Giannina Gaslini; Italia. University of Genoa; Italia ; Fil: Vandrovcova, Jana. University College London; Estados Unidos ; Fil: Cutrupi, Maria Concetta. University of Messina; Italia ; Fil: Chimenz, Roberto. University of Messina; Italia ; Fil: David, Emanuele. Papardo University Hospital; Italia ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0002-9297 |
| العلاقة: | info:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0002929719300618Test; http://hdl.handle.net/11336/160046Test; 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; CONICET Digital; CONICET |
| الإتاحة: | https://doi.org/10.1016/j.ajhg.2019.02.016Test http://hdl.handle.net/11336/160046Test |
| حقوق: | info:eu-repo/semantics/openAccess ; https://creativecommons.org/licenses/by-nc-sa/2.5/arTest/ |
| رقم الانضمام: | edsbas.FDB1904 |
| قاعدة البيانات: | BASE |
| تدمد: | 00029297 |
|---|