GRIN2B encephalopathy: Novel findings on phenotype, variant clustering, functional consequences and treatment aspects
dc.date.accessioned | 2018-08-21T12:32:02Z | |
dc.date.available | 2018-08-21T12:32:02Z | |
dc.date.created | 2017-10-09T13:56:09Z | |
dc.date.issued | 2017 | |
dc.identifier.citation | Platzer, Konrad Yuan, Hongjie Schütz, Hannah Winschel, Alexander Chen, Wenjuan Hu, Chun Kusumoto, Hirofumi Heyne, Henrike O. Helbig, Katherine L. Tang, Sha Willing, Marcia C. Tinkle, Brad T. Adams, Darius J. Depienne, Christel Keren, Boris Mignot, Cyril Frengen, Eirik Strømme, Petter Biskup, Saskia Docker, Dennis Strom, Tim M. Mefford, Heather C. Myers, Candace T. Muir, Alison M. LaCroix, Amy Sadleir, Lynette Scheffer, Ingrid E. Brilstra, Eva van Haelst, Mieke M. van der Smagt, Jasper J. Bok, Levinus A. Møller, Rikke S. Jensen, Uffe B. Millichap, John J. Berg, Anne T. Goldberg, Ethan M. De Bie, Isabelle Fox, Stephanie Major, Philippe Jones, Julie R. Zackai, Elaine H. Abou Jamra, Rami Rolfs, Arndt Leventer, Richard J. Lawson, John A. Roscioli, Tony Jansen, Floor E. Ranza, Emmanuelle Korff, Christian M. Lehesjoki, Anna-Elina Courage, Carolina Linnankivi, Tarja Smith, Douglas R. Stanley, Christine Mintz, Mark McKnight, Dianalee Decker, Amy Tan, Wen-Hann Tarnopolsky, Mark A. Brady, Lauren I. Wolff, Markus Dondit, Lutz Pedro, Helio F. Parisotto, Sarah E. Jones, Kelly L. Patel, Anup D. Franz, David N. Vanzo, Rena Marco, Elysa Ranells, Judith D. Di Donato, Nataliya Dobyns, William B. Laube, Bodo Traynelis, Stephen F. Lemke, Johannes R. . GRIN2B encephalopathy: Novel findings on phenotype, variant clustering, functional consequences and treatment aspects. Journal of Medical Genetics. 2017, 54(7), 460-470 | |
dc.identifier.uri | http://hdl.handle.net/10852/63295 | |
dc.description.abstract | Background: We aimed for a comprehensive delineation of genetic, functional and phenotypic aspects of GRIN2B encephalopathy and explored potential prospects of personalised medicine. Methods: Data of 48 individuals with de novo GRIN2B variants were collected from several diagnostic and research cohorts, as well as from 43 patients from the literature. Functional consequences and response to memantine treatment were investigated in vitro and eventually translated into patient care. Results: Overall, de novo variants in 86 patients were classified as pathogenic/likely pathogenic. Patients presented with neurodevelopmental disorders and a spectrum of hypotonia, movement disorder, cortical visual impairment, cerebral volume loss and epilepsy. Six patients presented with a consistent malformation of cortical development (MCD) intermediate between tubulinopathies and polymicrogyria. Missense variants cluster in transmembrane segments and ligand-binding sites. Functional consequences of variants were diverse, revealing various potential gain-of-function and loss-of-function mechanisms and a retained sensitivity to the use-dependent blocker memantine. However, an objectifiable beneficial treatment response in the respective patients still remains to be demonstrated. Conclusions: In addition to previously known features of intellectual disability, epilepsy and autism, we found evidence that GRIN2B encephalopathy is also frequently associated with movement disorder, cortical visual impairment and MCD revealing novel phenotypic consequences of channelopathies. | en_US |
dc.language | EN | |
dc.publisher | BMJ Publishing Group. | |
dc.title | GRIN2B encephalopathy: Novel findings on phenotype, variant clustering, functional consequences and treatment aspects | en_US |
dc.type | Journal article | en_US |
dc.creator.author | Platzer, Konrad | |
dc.creator.author | Yuan, Hongjie | |
dc.creator.author | Schütz, Hannah | |
dc.creator.author | Winschel, Alexander | |
dc.creator.author | Chen, Wenjuan | |
dc.creator.author | Hu, Chun | |
dc.creator.author | Kusumoto, Hirofumi | |
dc.creator.author | Heyne, Henrike O. | |
dc.creator.author | Helbig, Katherine L. | |
dc.creator.author | Tang, Sha | |
dc.creator.author | Willing, Marcia C. | |
dc.creator.author | Tinkle, Brad T. | |
dc.creator.author | Adams, Darius J. | |
dc.creator.author | Depienne, Christel | |
dc.creator.author | Keren, Boris | |
dc.creator.author | Mignot, Cyril | |
dc.creator.author | Frengen, Eirik | |
dc.creator.author | Strømme, Petter | |
dc.creator.author | Biskup, Saskia | |
dc.creator.author | Docker, Dennis | |
dc.creator.author | Strom, Tim M. | |
dc.creator.author | Mefford, Heather C. | |
dc.creator.author | Myers, Candace T. | |
dc.creator.author | Muir, Alison M. | |
dc.creator.author | LaCroix, Amy | |
dc.creator.author | Sadleir, Lynette | |
dc.creator.author | Scheffer, Ingrid E. | |
dc.creator.author | Brilstra, Eva | |
dc.creator.author | van Haelst, Mieke M. | |
dc.creator.author | van der Smagt, Jasper J. | |
dc.creator.author | Bok, Levinus A. | |
dc.creator.author | Møller, Rikke S. | |
dc.creator.author | Jensen, Uffe B. | |
dc.creator.author | Millichap, John J. | |
dc.creator.author | Berg, Anne T. | |
dc.creator.author | Goldberg, Ethan M. | |
dc.creator.author | De Bie, Isabelle | |
dc.creator.author | Fox, Stephanie | |
dc.creator.author | Major, Philippe | |
dc.creator.author | Jones, Julie R. | |
dc.creator.author | Zackai, Elaine H. | |
dc.creator.author | Abou Jamra, Rami | |
dc.creator.author | Rolfs, Arndt | |
dc.creator.author | Leventer, Richard J. | |
dc.creator.author | Lawson, John A. | |
dc.creator.author | Roscioli, Tony | |
dc.creator.author | Jansen, Floor E. | |
dc.creator.author | Ranza, Emmanuelle | |
dc.creator.author | Korff, Christian M. | |
dc.creator.author | Lehesjoki, Anna-Elina | |
dc.creator.author | Courage, Carolina | |
dc.creator.author | Linnankivi, Tarja | |
dc.creator.author | Smith, Douglas R. | |
dc.creator.author | Stanley, Christine | |
dc.creator.author | Mintz, Mark | |
dc.creator.author | McKnight, Dianalee | |
dc.creator.author | Decker, Amy | |
dc.creator.author | Tan, Wen-Hann | |
dc.creator.author | Tarnopolsky, Mark A. | |
dc.creator.author | Brady, Lauren I. | |
dc.creator.author | Wolff, Markus | |
dc.creator.author | Dondit, Lutz | |
dc.creator.author | Pedro, Helio F. | |
dc.creator.author | Parisotto, Sarah E. | |
dc.creator.author | Jones, Kelly L. | |
dc.creator.author | Patel, Anup D. | |
dc.creator.author | Franz, David N. | |
dc.creator.author | Vanzo, Rena | |
dc.creator.author | Marco, Elysa | |
dc.creator.author | Ranells, Judith D. | |
dc.creator.author | Di Donato, Nataliya | |
dc.creator.author | Dobyns, William B. | |
dc.creator.author | Laube, Bodo | |
dc.creator.author | Traynelis, Stephen F. | |
dc.creator.author | Lemke, Johannes R. | |
cristin.unitcode | 185,53,18,10 | |
cristin.unitname | Avdeling for medisinsk genetikk | |
cristin.ispublished | true | |
cristin.fulltext | postprint | |
cristin.qualitycode | 2 | |
dc.identifier.cristin | 1503403 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Journal of Medical Genetics&rft.volume=54&rft.spage=460&rft.date=2017 | |
dc.identifier.jtitle | Journal of Medical Genetics | |
dc.identifier.volume | 54 | |
dc.identifier.issue | 7 | |
dc.identifier.startpage | 460 | |
dc.identifier.endpage | 470 | |
dc.identifier.doi | http://dx.doi.org/10.1136/jmedgenet-2016-104509 | |
dc.identifier.urn | URN:NBN:no-65849 | |
dc.type.document | Tidsskriftartikkel | en_US |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 0022-2593 | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/63295/2/GRINBencephalopathy.pdf | |
dc.type.version | AcceptedVersion |
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