Welcome to the UPF Digital Repository

Autosomal recessive variants in TUBGCP2 alter the γ-tubulin ring complex leading to neurodevelopmental disease

Show simple item record

dc.contributor.author Gungor, Serdal
dc.contributor.author Aranguren-Ibáñez, Álvaro
dc.contributor.author Laurie, Steven, 1973-
dc.contributor.author Beltran, Sergi
dc.contributor.author Vernos, Isabelle, 1959-
dc.contributor.author Horvath, Rita
dc.date.accessioned 2021-05-19T11:24:52Z
dc.date.available 2021-05-19T11:24:52Z
dc.date.issued 2020
dc.identifier.citation Gungor S, Oktay Y, Hiz S, Aranguren-Ibáñez A, Kalafatcilar I, Yaramis A et al. Autosomal recessive variants in TUBGCP2 alter the γ-tubulin ring complex leading to neurodevelopmental disease. iScience. 2020 Dec 30;24(1):101948. DOI: 10.1016/j.isci.2020.101948
dc.identifier.issn 2589-0042
dc.identifier.uri http://hdl.handle.net/10230/47613
dc.description.abstract Microtubules help building the cytoskeleton of neurons and other cells. Several components of the gamma-tubulin (γ-tubulin) complex have been previously reported in human neurodevelopmental diseases. We describe two siblings from a consanguineous Turkish family with dysmorphic features, developmental delay, brain malformation, and epilepsy carrying a homozygous mutation (p.Glu311Lys) in TUBGCP2 encoding the γ-tubulin complex 2 (GCP2) protein. This variant is predicted to disrupt the electrostatic interaction of GCP2 with GCP3. In primary fibroblasts carrying the variant, we observed a faint delocalization of γ-tubulin during the cell cycle but normal GCP2 protein levels. Through mass spectrometry, we observed dysregulation of multiple proteins involved in the assembly and organization of the cytoskeleton and the extracellular matrix, controlling cellular adhesion and of proteins crucial for neuronal homeostasis including axon guidance. In summary, our functional and proteomic studies link TUBGCP2 and the γ-tubulin complex to the development of the central nervous system in humans.
dc.description.sponsorship This study was supported by the Turkish Scientific and Research Council (TÜBITAK) research grant 216S771. Y.O. is supported by Turkish Academy of Sciences Young Investigator Programme (TUBA-GEBIP). R.H. is a Wellcome Trust Investigator (109915/Z/15/Z), who receives support from the Wellcome Centre for Mitochondrial Research (203105/Z/16/Z), Medical Research Council (UK) (MR/N025431/1), the European Research Council (309548), the Wellcome Trust Pathfinder Scheme (201064/Z/16/Z), the Newton Fund (UK/Turkey, MR/N027302/1), Evelyn Trust, Lily Foundation, and MRC strategic award to establish an International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD, MR/S005021/1). A.R. received financial support by the French Muscular Dystrophy Association (AFM-Téléthon; grant 21466). Sequence analysis was provided by the Broad Institute of MIT and Harvard Center for Mendelian Genomics and was funded by the National Human Genome Research Institute (UM1 HG008900 and R01 HG009141) with supplemental funding provided by the National Heart, Lung, and Blood Institute under the Trans-Omics for Precision Medicine (TOPMed) program and the National Eye Institute. I.V. and Á.A.I. were supported by the CRG internal funds, grant 2017 SGR 478 from AGAUR and grant PGC2018-096976-B-I00 from the Spanish ministry of science, innovation and universities. H.L. receives support from the Canadian Institutes of Health Research (Foundation Grant FDN-167281), the Canadian Institutes of Health Research and Muscular Dystrophy Canada (Network Catalyst Grant for NMD4C), the Canada Foundation for Innovation (CFI-JELF 38412), and the Canada Research Chairs program (Canada Research Chair in Neuromuscular Genomics and Health, 950-232279). Data were analyzed using the RD-Connect Genome-Phenome Analysis Platform developed under FP7/2007-2013 funded project (grant agreement nº 305444) and funding from European Joint Programme in Rare Disease (EJP-RD) and INB/ELIXIR-ES
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Cell Press
dc.rights © 2020 Serdal Gungor et al. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.other Genètica
dc.subject.other Proteïnes
dc.subject.other Malalties del neurodesenvolupament
dc.title Autosomal recessive variants in TUBGCP2 alter the γ-tubulin ring complex leading to neurodevelopmental disease
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1016/j.isci.2020.101948
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/305444
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


This item appears in the following Collection(s)

Show simple item record

Search DSpace

Advanced Search


My Account


In collaboration with Compliant to Partaking