Duplications at 19q13.33 in patients with neurodevelopmental disorders

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dc.contributor.authorPérez-Palma, E.
dc.contributor.authorSaarentaus, E.
dc.contributor.authorRavoet, M.
dc.contributor.authorDe Ferrari, G.V.
dc.contributor.authorNürnberg, P.
dc.contributor.authorIsidor, B.
dc.contributor.authorNeubauer, B.A.
dc.contributor.authorLal, D.
dc.date.accessioned2019-06-19T20:31:37Z
dc.date.available2019-06-19T20:31:37Z
dc.date.issued2018-02
dc.descriptionIndexación: Scopus.es_ES
dc.descriptionThe authors thank all the clinicians, patients, and their families. This study makes use of data generated by the DECIPHER community. A full list of centers who contributed to the generation of the data is available from http://decipher.sanger.ac.uk and via email from decipher@ sanger.ac.uk. Funding for the project was provided by the Wellcome Trust.
dc.descriptionEduardo Pérez-Palma was supported by the Chilean Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT) regular grant number 1140353 to Giancarlo V. De Ferrari. Dennis Lal received funds from the German Academic Exchange Service (DAAD), grant number 57073880. Bernd A. Neubauer received funding from the Deutsche For-schungsgemeinschaft (Ne 416/5-1).
dc.descriptionE. Pérez-Palma has received research support from Fondo Nacional de Ciencia y Tecnología (FONDECYT), Chile. E. Saarentaus has received research support from the Institute for Molecular Medicine Finland (FIMM) and Sven-ska Studiefonden. M. Ravoet has been involved in clinical procedures/imaging studies at the Center of Human Genetics, Cliniques Universitaires St-Luc (10%), 2016. G.V. De Ferrari has received research support from Fondo Nacional de Ciencia y Tecnología (FONDECYT), Chile, and CON-ICYT. Chile. P. Nuernberg is a founder, CEO, and shareholder of ATLAS Biolabs GmbH (ATLAS Biolabs GmbH is a service provider for genomic analyses). B. Isidor reports no disclosures. B. Neubauer has served on the scientificadvisory boards of and has received travel funding/speaker honoraria from Eisai, Bial, and UCB Pharma; has served on the editorial board of Neuropediatrics; and has received research support from DFG 416/5-1 (German national funding agency). D. Lal reports no disclosures. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/NG.
dc.description.abstractObjective: After the recent publication of the first patients with disease-associated missense variants in the GRIN2D gene, we evaluate the effect of copy number variants (CNVs) overlapping this gene toward the presentation of neurodevelopmental disorders (NDDs). Methods: We explored ClinVar (numberofCNVs= 50,794) and DECIPHER (numberofCNVs=28,085) clinical databases of genomic variations for patients with copy number changes overlapping the GRIN2D gene at the 19q13.33 locus and evaluated their respective phenotype alongside their frequency, gene content, and expression, with publicly available reference databases. Results: We identified 11 patients with microduplications at the 19q13.33 locus. The majority of CNVs arose de novo, and comparable CNVs are not present in control databases. All patients were reported to have NDDs and dysmorphic features as the most common clinical phenotype (N = 8/11), followed by seizures (N = 6/11) and intellectual disability (N = 5/11). All duplications shared a consensus region of 405 kb overlapping 13 genes. After screening for duplication tolerance in control populations, positive gene brain expression, and gene dosage sensitivity analysis, we highlight 4 genes for future evaluation: CARD8, C19orf68, KDELR1, and GRIN2D, which are promising candidates for disease causality. Furthermore, investigation of the literature especially supports GRIN2D as the best candidate gene. Conclusions: Our study presents dup19q13.33 as a novel duplication syndrome locus associated with NDDs. CARD8, C19orf68, KDELR1, and GRIN2D are promising candidates for functional follow-up. Copyright © 2018 The Author(s).es_ES
dc.description.urihttps://ng.neurology.org/content/4/1/e210
dc.identifier.citationNeurology: Genetics, 4(1), art. no. e210.es_ES
dc.identifier.issn2376-7839
dc.identifier.otherDOI: 10.1212/NXG.0000000000000210
dc.identifier.urihttp://repositorio.unab.cl/xmlui/handle/ria/9243
dc.language.isoenes_ES
dc.publisherLippincott Williams and Wilkinses_ES
dc.subjectAll Epilepsy/Seizureses_ES
dc.subjectDevelopmental disorderses_ES
dc.subjectIon channel gene defectses_ES
dc.titleDuplications at 19q13.33 in patients with neurodevelopmental disorderses_ES
dc.typeArtículoes_ES
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