UCL  IRIS
Institutional Research Information Service
UCL Logo
Please report any queries concerning the funding data grouped in the sections named "Externally Awarded" or "Internally Disbursed" (shown on the profile page) to your Research Finance Administrator. Your can find your Research Finance Administrator at https://www.ucl.ac.uk/finance/research/rs-contacts.php by entering your department
Please report any queries concerning the student data shown on the profile page to:

Email: portico-services@ucl.ac.uk

Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
Publication Detail
Mutations in the Neuronal Vesicular SNARE VAMP2 Affect Synaptic Membrane Fusion and Impair Human Neurodevelopment
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Article
  • Authors:
    Salpietro V, Malintan NT, Llano-Rivas I, Spaeth CG, Efthymiou S, Striano P, Vandrovcova J, Cutrupi MC, Chimenz R, David E, Di Rosa G, Marce-Grau A, Raspall-Chaure M, Martin-Hernandez E, Zara F, Minetti C, Deciphering Developmental Disorders Study , SYNAPS Study Group , Bello OD, De Zorzi R, Fortuna S, Dauber A, Alkhawaja M, Sultan T, Mankad K, Vitobello A, Thomas Q, Mau-Them FT, Faivre L, Martinez-Azorin F, Prada CE, Macaya A, Kullmann DM, Rothman JE, Krishnakumar SS, Houlden H
  • Publisher:
    Elsevier
  • Publication date:
    04/04/2019
  • Pagination:
    721, 730
  • Journal:
    American Journal of Human Genetics
  • Volume:
    104
  • Issue:
    4
  • Status:
    Published
  • Country:
    United States
  • Print ISSN:
    0002-9297
  • PII:
    S0002-9297(19)30061-8
  • Language:
    eng
  • Keywords:
    SNARE, VAMP2, autism, epilepsy, movement disorders, neurodevelopmental disorders, neuronal exocytosis, synaptobrevin, synaptopathy, vesicle fusion
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.
Publication data is maintained in RPS. Visit https://rps.ucl.ac.uk
 More search options
UCL Researchers Show More
Author
Clinical & Experimental Epilepsy
Author
Clinical & Experimental Epilepsy
Author
Department of Neuromuscular Diseases
Author
Department of Neuromuscular Diseases
Author
Clinical & Experimental Epilepsy
Author
Clinical & Experimental Epilepsy
Author
Clinical & Experimental Epilepsy
Author
Clinical & Experimental Epilepsy
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by