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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorVerdura, Edgard
dc.contributor.authorRodriguez-Palmero Seuma, Agusti
dc.contributor.authorVélez Santamaria, Valentina
dc.contributor.authorPlanas Serra, Laura
dc.contributor.authorde la Calle, Irene
dc.contributor.authorRaspall Chaure, Miquel
dc.date.accessioned2022-06-13T13:29:41Z
dc.date.available2022-06-13T13:29:41Z
dc.date.issued2021-09
dc.identifier.citationVerdura E, Rodríguez-Palmero A, Vélez-Santamaria V, Planas-Serra L, de La Calle I, Raspall-Chaure M, et al. Biallelic PI4KA variants cause a novel neurodevelopmental syndrome with hypomyelinating leukodystrophy. Brain. 2021 Sep;144(9):2659–69.
dc.identifier.issn1460-2156
dc.identifier.urihttp://hdl.handle.net/11351/7675
dc.descriptionHypomyelinating leukodystrophy; Inborn errors of metabolism; Phosphoinositol
dc.description.abstractPhosphoinositides are lipids that play a critical role in processes such as cellular signalling, ion channel activity and membrane trafficking. When mutated, several genes that encode proteins that participate in the metabolism of these lipids give rise to neurological or developmental phenotypes. PI4KA is a phosphoinositide kinase that is highly expressed in the brain and is essential for life. Here we used whole exome or genome sequencing to identify 10 unrelated patients harbouring biallelic variants in PI4KA that caused a spectrum of conditions ranging from severe global neurodevelopmental delay with hypomyelination and developmental brain abnormalities to pure spastic paraplegia. Some patients presented immunological deficits or genito-urinary abnormalities. Functional analyses by western blotting and immunofluorescence showed decreased PI4KA levels in the patients’ fibroblasts. Immunofluorescence and targeted lipidomics indicated that PI4KA activity was diminished in fibroblasts and peripheral blood mononuclear cells. In conclusion, we report a novel severe metabolic disorder caused by PI4KA malfunction, highlighting the importance of phosphoinositide signalling in human brain development and the myelin sheath.
dc.language.isoeng
dc.publisherOxford University Press
dc.relation.ispartofseriesBrain;144(9)
dc.rightsAttribution-NonCommercial 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.sourceScientia
dc.subjectPediatria
dc.subjectSistema nerviós - Malalties - Aspectes genètics
dc.subjectMielina - Malalties - Aspectes genètics
dc.subject.meshNeurodevelopmental Disorders
dc.subject.mesh/genetics
dc.subject.meshPediatrics
dc.subject.meshHereditary Central Nervous System Demyelinating Diseases
dc.titleBiallelic PI4KA variants cause a novel neurodevelopmental syndrome with hypomyelinating leukodystrophy
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1093/brain/awab124
dc.subject.decstrastornos del desarrollo neurológico
dc.subject.decs/genética
dc.subject.decspediatría
dc.subject.decsenfermedades desmielinizantes hereditarias del sistema nervioso central
dc.relation.publishversionhttps://doi.org/10.1093/brain/awab124
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Verdura E, Planas-Serra L] Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08908, Barcelona, Catalonia, Spain. Centre for Biomedical Research in Network on Rare Diseases (CIBERER), Instituto de Salud Carlos III, 28029, Madrid, Spain. [Rodríguez-Palmero A] Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08908, Barcelona, Catalonia, Spain. Pediatric Neurology Unit, Department of Pediatrics, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Catalonia, Spain. [Vélez-Santamaria V] Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08908, Barcelona, Catalonia, Spain. Neuromuscular Unit, Neurology Department, Hospital Universitari de Bellvitge, Universitat de Barcelona, L’Hospitalet de Llobregat, Barcelona, Spain. [de la Calle I] Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08908, Barcelona, Catalonia, Spain. [Raspall-Chaure M] Grup de Recerca en Neurologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei de Neurologia Pediàtrica, Vall d’Hebron Hospital Universitari, Barcelona, Spain
dc.identifier.pmid34415322
dc.identifier.wos000733722200027
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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