2019
Mutations in the Neuronal Vesicular SNARE VAMP2 Affect Synaptic Membrane Fusion and Impair Human Neurodevelopment
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, Study D, Group S, Salpietro V, Efthymiou S, Kriouile Y, Khorassani M, Aguennouz M, Karashova B, Avdjieva D, Kathom H, Tincheva R, Van Maldergem L, Nachbauer W, Boesch S, Arning L, Timmann D, Cormand B, Pérez-Dueñas B, Di Rosa G, Pironti E, Goraya J, Sultan T, Kirmani S, Ibrahim S, Jan F, Mine J, Banu S, Veggiotti P, Ferrari M, Verrotti A, Marseglia G, Savasta S, Garavaglia B, Scuderi C, Borgione E, Dipasquale V, Cutrupi M, Portaro S, Sanchez B, Pineda-Marfa’ M, Munell F, Macaya A, Boles R, Heimer G, Papacostas S, Manole A, Malintan N, Zanetti M, Hanna M, Rothman J, Kullmann D, Houlden H, Bello O, De Zorzi R, Fortuna S, Dauber A, Alkhawaja M, Sultan T, Mankad K, Vitobello A, Thomas Q, Mau-Them F, Faivre L, Martinez-Azorin F, Prada C, Macaya A, Kullmann D, Rothman J, Krishnakumar S, Houlden H. Mutations in the Neuronal Vesicular SNARE VAMP2 Affect Synaptic Membrane Fusion and Impair Human Neurodevelopment. American Journal Of Human Genetics 2019, 104: 721-730. PMID: 30929742, PMCID: PMC6451933, DOI: 10.1016/j.ajhg.2019.02.016.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAutistic DisorderBrainChildChild, PreschoolEpilepsyExocytosisFemaleHeterozygoteHumansIntellectual DisabilityLipidsMagnetic Resonance ImagingMaleMembrane FusionMovement DisordersMuscle HypotoniaMutationNeurodevelopmental DisordersNeuronsNeurotransmitter AgentsPhenotypeProtein DomainsR-SNARE ProteinsSynapsesVesicle-Associated Membrane Protein 2ConceptsNon-synonymous variantsDe novo mutationsSNARE protein VAMP2Synaptic membrane fusionC-terminal regionNovo mutationsSNARE motifSynaptosomal-associated protein 25C-terminusMembrane fusionVAMP2Vesicle fusionHuman brain developmentAcid deletionSynaptic vesiclesVesicular exocytosisHeterozygous de novo mutationsProtein 25Hyperkinetic movement disordersAdditional neurological featuresHuman neurodevelopmentCentral visual impairmentDisease mechanismsUnrelated individualsMutations
2017
Mutations in Membrin/GOSR2 Reveal Stringent Secretory Pathway Demands of Dendritic Growth and Synaptic Integrity
Praschberger R, Lowe SA, Malintan NT, Giachello CNG, Patel N, Houlden H, Kullmann DM, Baines RA, Usowicz MM, Krishnakumar SS, Hodge JJL, Rothman JE, Jepson JEC. Mutations in Membrin/GOSR2 Reveal Stringent Secretory Pathway Demands of Dendritic Growth and Synaptic Integrity. Cell Reports 2017, 21: 97-109. PMID: 28978487, PMCID: PMC5640804, DOI: 10.1016/j.celrep.2017.09.004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDendritesDrosophila melanogasterFemaleFibroblastsGene ExpressionGenetic Association StudiesGolgi ApparatusHumansMaleMembrane FusionMutationMyoclonic Epilepsies, ProgressivePhenotypePrimary Cell CultureQb-SNARE ProteinsRecombinant ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSecretory PathwaySynapsesYoung AdultConceptsMembrane fusionGolgi membrane fusionProgressive myoclonus epilepsyGenotype-phenotype relationshipsPresynaptic cytoskeletonEssential proteinsDrosophila modelMembrinMutationsPathogenic mutationsSynaptic functionProteinMyoclonus epilepsyExplanatory basisCytoskeletonGrowthSynaptic integrityPathway deficitsNervous systemMulti-layered strategySnareFusionFragmentationHomozygous mutations in VAMP1 cause a presynaptic congenital myasthenic syndrome
Salpietro V, Lin W, Delle Vedove A, Storbeck M, Liu Y, Efthymiou S, Manole A, Wiethoff S, Ye Q, Saggar A, McElreavey K, Krishnakumar SS, Group S, Pitt M, Bello OD, Rothman JE, Basel‐Vanagaite L, Hubshman MW, Aharoni S, Manzur AY, Wirth B, Houlden H. Homozygous mutations in VAMP1 cause a presynaptic congenital myasthenic syndrome. Annals Of Neurology 2017, 81: 597-603. PMID: 28253535, PMCID: PMC5413866, DOI: 10.1002/ana.24905.Peer-Reviewed Original ResearchConceptsPresynaptic congenital myasthenic syndromeCongenital myasthenic syndromePresynaptic impairmentMyasthenic syndromeLow compound muscle action potentialsNeuromuscular junctionCompound muscle action potentialPresynaptic neuromuscular junctionHomozygous mutationMuscle action potentialsAnn NeurolNMJ transmissionElectrodiagnostic examinationNeurophysiological featuresAction potentialsLew/Homozygous variantMRNA levelsSyndromeWhole exomeImpairmentVAMP1Kuwaiti familyNonsense mutationMutations