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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorAguilera, Cinthia
dc.contributor.authorHümmer, Stefan
dc.contributor.authorMasanas Jimenez, Marc
dc.contributor.authorGabau, Elisabeth
dc.contributor.authorGuitart, Miriam
dc.contributor.authorJeyaprakash, A. Arockia
dc.contributor.authorSegura Ginard, Miguel
dc.contributor.authorSantamaria Margalef, Anna
dc.contributor.authorRuiz, Anna
dc.date.accessioned2021-12-17T11:30:35Z
dc.date.available2021-12-17T11:30:35Z
dc.date.issued2021-05-26
dc.identifier.citationAguilera C, Hümmer S, Masanas M, Gabau E, Guitart M, Jeyaprakash AA, et al. The Novel KIF1A Missense Variant (R169T) Strongly Reduces Microtubule Stimulated ATPase Activity and Is Associated With NESCAV Syndrome. Front Neurosci. 2021 May 26;15:618098.
dc.identifier.issn1662-453X
dc.identifier.urihttp://hdl.handle.net/11351/6709
dc.descriptionNESCAV syndrome; Kinesin; Microtubule
dc.description.abstractKIF1A is a microtubule-dependent motor protein responsible for fast anterograde transport of synaptic vesicle precursors in neurons. Pathogenic variants in KIF1A have been associated with a wide spectrum of neurological disorders. Here, we report a patient presenting a severe neurodevelopmental disorder carrying a novel de novo missense variant p.Arg169Thr (R169T) in the KIF1A motor domain. The clinical features present in our patient match with those reported for NESCAV syndrome including severe developmental delay, spastic paraparesis, motor sensory neuropathy, bilateral optic nerve atrophy, progressive cerebellar atrophy, epilepsy, ataxia, and hypotonia. Here, we demonstrate that the microtubule-stimulated ATPase activity of the KIF1A is strongly reduced in the motor domain of the R169T variant. Supporting this, in silico structural modeling suggests that this variant impairs the interaction of the KIF1A motor domain with microtubules. The characterization of the molecular effect of the R169T variant on the KIF1A protein together with the presence of the typical clinical features indicates its causal pathogenic effect.
dc.language.isoeng
dc.publisherFrontiers Media
dc.relation.ispartofseriesFrontiers in Neuroscience;15
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientia
dc.subjectMalalties - Aspectes moleculars
dc.subjectNeurobiologia molecular
dc.subjectSistema nerviós - Malalties
dc.subject.meshNervous System Diseases
dc.subject.mesh/pathology
dc.subject.meshModels, Molecular
dc.titleThe Novel KIF1A Missense Variant (R169T) Strongly Reduces Microtubule Stimulated ATPase Activity and Is Associated With NESCAV Syndrome
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.3389/fnins.2021.618098
dc.subject.decsenfermedades del sistema nervioso
dc.subject.decs/patología
dc.subject.decsmodelos moleculares
dc.relation.publishversionhttps://doi.org/10.3389/fnins.2021.618098
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Aguilera C, Guitart M, Ruiz A] Genetics Laboratory, UDIAT-Centre Diagnòstic, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Spain. [Hümmer S] Grup de Patologia Molecular Translacional, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Spanish Biomedical Research Network Centre in Oncology (CIBERONC), Madrid, Spain. [Masanas M, Segura MF] Grup de Recerca Translacional en Càncer en la Infància i l’Adolescència, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Gabau E] Paediatric Unit, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Spain. [Jeyaprakash AA] Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom. [Santamaria A] Laboratori de Càncer i Cicle Cel•lular, Grup de Recerca Biomèdica en Urologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain
dc.identifier.pmid34121983
dc.identifier.wos000658890200001
dc.relation.projectidinfo:eu-repo/grantAgreement/ES/PE2013-2016/PI16%2F01411
dc.relation.projectidinfo:eu-repo/grantAgreement/ES/PE2013-2016/CB16%2F12%2F00363
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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