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DC Field | Value | Language |
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dc.contributor.author | Ambrosini, Elena | - |
dc.contributor.author | Sicca, Federico | - |
dc.contributor.author | Brignone, Maria Stefania | - |
dc.contributor.author | D'Adamo, Maria Cristina | - |
dc.contributor.author | Napolitano, Carlo | - |
dc.contributor.author | Servettini, Ilenio | - |
dc.contributor.author | Moro, Francesca | - |
dc.contributor.author | Ruan, Yanfei | - |
dc.contributor.author | Guglielmi, Luca | - |
dc.contributor.author | Pieroni, Stefania | - |
dc.contributor.author | Servillo, Giuseppe | - |
dc.contributor.author | Lanciotti, Angela | - |
dc.contributor.author | Valvo, Giulia | - |
dc.contributor.author | Catacuzzeno, Luigi | - |
dc.contributor.author | Franciolini, Fabio | - |
dc.contributor.author | Molinari, Paola | - |
dc.contributor.author | Marchese, Maria | - |
dc.contributor.author | Grottesi, Alessandro | - |
dc.contributor.author | Guerrini, Renzo | - |
dc.contributor.author | Santorelli, Filippo Maria | - |
dc.contributor.author | Priori, Silvia Giuliana | - |
dc.contributor.author | Pessia, Mauro | - |
dc.date.accessioned | 2018-03-26T11:53:03Z | - |
dc.date.available | 2018-03-26T11:53:03Z | - |
dc.date.issued | 2014 | - |
dc.identifier.citation | Ambrosini, E., Sicca, F., Brignone, M. S., D'adamo, M. C., Napolitano, C., Servettini, I.,...Pessia, M. (2014). Genetically induced dysfunctions of Kir2.1 channels: implications for short QT3 syndrome and autism-epilepsy phenotype. Human Molecular Genetics, 23(18), 4875-4886. | en_GB |
dc.identifier.uri | https://www.um.edu.mt/library/oar//handle/123456789/28279 | - |
dc.description.abstract | Short QT3 syndrome (SQT3S) is a cardiac disorder characterized by a high risk of mortality and associated with mutations in Kir2.1 (KCNJ2) channels. The molecular mechanisms leading to channel dysfunction, cardiac rhythm disturbances and neurodevelopmental disorders, potentially associated with SQT3S, remain incompletely understood. Here, we report on monozygotic twins displaying a short QT interval on electrocardiogram recordings and autism-epilepsy phenotype. Genetic screening identified a novel KCNJ2 variant in Kir2.1 that (i) enhanced the channel's surface expression and stability at the plasma membrane, (ii) reduced protein ubiquitylation and degradation, (iii) altered protein compartmentalization in lipid rafts by targeting more channels to cholesterol-poor domains and (iv) reduced interactions with caveolin 2. Importantly, our study reveals novel physiological mechanisms concerning wild-type Kir2.1 channel processing by the cell, such as binding to both caveolin 1 and 2, protein degradation through the ubiquitin-proteasome pathway; in addition, it uncovers a potential multifunctional site that controls Kir2.1 surface expression, protein half-life and partitioning to lipid rafts. The reported mechanisms emerge as crucial also for proper astrocyte function, suggesting the need for a neuropsychiatric evaluation in patients with SQT3S and offering new opportunities for disease management. | en_GB |
dc.language.iso | en | en_GB |
dc.publisher | Oxford University Press | en_GB |
dc.rights | info:eu-repo/semantics/restrictedAccess | en_GB |
dc.subject | Potassium channels | en_GB |
dc.subject | Astrocytomas | en_GB |
dc.subject | Autism spectrum disorders | en_GB |
dc.subject | Autism | en_GB |
dc.subject | Epilepsy | en_GB |
dc.title | Genetically induced dysfunctions of Kir2.1 channels : implications for short QT3 syndrome and autism-epilepsy phenotype | en_GB |
dc.type | article | en_GB |
dc.rights.holder | The copyright of this work belongs to the author(s)/publisher. The rights of this work are as defined by the appropriate Copyright Legislation or as modified by any successive legislation. Users may access this work and can make use of the information contained in accordance with the Copyright Legislation provided that the author must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the prior permission of the copyright holder. | en_GB |
dc.description.reviewed | peer-reviewed | en_GB |
dc.identifier.doi | 10.1093/hmg/ddu201 | - |
dc.publication.title | Human Molecular Genetics | en_GB |
Appears in Collections: | Scholarly Works - FacM&SPB |
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Genetically_induced_dysfunctions_of_Kir2.1_channels_2014.pdf Restricted Access | 811.82 kB | Adobe PDF | View/Open Request a copy |
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