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dc.rights.licenseopenen_US
dc.contributor.authorDE BOER, Elke
dc.contributor.authorOCKELOEN, Charlotte W.
dc.contributor.authorMATALONGA, Leslie
dc.contributor.authorHORVATH, Rita
dc.contributor.authorSOLVE-RD SNV-INDEL, Working Group
dc.contributor.authorRODENBURG, Richard J.
dc.contributor.authorCOENEN, Marieke J. H.
dc.contributor.authorJANSSEN, Mirian
dc.contributor.authorHENSSEN, Dylan
dc.contributor.authorGILISSEN, Christian
dc.contributor.authorSTEYAERT, Wouter
dc.contributor.authorPARAMONOV, Ida
dc.contributor.authorSOLVE-RD, DITF-ITHACA
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorTRIMOUILLE, Aurelien
dc.contributor.authorKLEEFSTRA, Tjitske
dc.contributor.authorVERLOES, Alain
dc.contributor.authorVISSERS, Lisenka E. L. M.
dc.date.accessioned2021-10-26T15:30:28Z
dc.date.available2021-10-26T15:30:28Z
dc.date.issued2021-06-01
dc.identifier.issn1476-5438 (online) 1018-4813 (print)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/117086
dc.description.abstractEnThe genetic etiology of intellectual disability remains elusive in almost half of all affected individuals. Within the Solve-RD consortium, systematic re-analysis of whole exome sequencing (WES) data from unresolved cases with (syndromic) intellectual disability (n = 1,472 probands) was performed. This re-analysis included variant calling of mitochondrial DNA (mtDNA) variants, although mtDNA is not specifically targeted in WES. We identified a functionally relevant mtDNA variant in MT-TL1 (NC_012920.1:m.3291T > C; NC_012920.1:n.62T > C), at a heteroplasmy level of 22% in whole blood, in a 23-year-old male with severe intellectual disability, epilepsy, episodic headaches with emesis, spastic tetraparesis, brain abnormalities, and feeding difficulties. Targeted validation in blood and urine supported pathogenicity, with heteroplasmy levels of 23% and 58% in index, and 4% and 17% in mother, respectively. Interestingly, not all phenotypic features observed in the index have been previously linked to this MT-TL1 variant, suggesting either broadening of the m.3291T > C-associated phenotype, or presence of a co-occurring disorder. Hence, our case highlights the importance of underappreciated mtDNA variants identifiable from WES data, especially for cases with atypical mitochondrial phenotypes and their relatives in the maternal line.
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.title.enA MT-TL1 variant identified by whole exome sequencing in an individual with intellectual disability, epilepsy, and spastic tetraparesis
dc.typeArticle de revueen_US
dc.identifier.doi10.1038/s41431-021-00900-2en_US
dc.subject.halSciences du Vivant [q-bio]/Médecine humaine et pathologieen_US
dc.identifier.pubmed34075211en_US
dc.description.sponsorshipEuropeEuropean Union’s Horizon 2020 research and innovation programmeen_US
bordeaux.journalEuropean Journal of Human Geneticsen_US
bordeaux.hal.laboratoriesMaladies Rares : Génétique et Métabolisme (MRGM) - UMR 1211en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDEuropean Research Councilen_US
bordeaux.identifier.funderIDEvelyn Trusten_US
bordeaux.identifier.funderIDNewton Funden_US
hal.identifierhal-03404614
hal.version1
hal.date.transferred2021-10-26T15:30:36Z
hal.exporttrue
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=European%20Journal%20of%20Human%20Genetics&rft.date=2021-06-01&rft.eissn=1476-5438%20(online)%201018-4813%20(print)&rft.issn=1476-5438%20(online)%201018-4813%20(print)&rft.au=DE%20BOER,%20Elke&OCKELOEN,%20Charlotte%20W.&MATALONGA,%20Leslie&HORVATH,%20Rita&SOLVE-RD%20SNV-INDEL,%20Working%20Group&rft.genre=article


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