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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.authorTrimouille, Aurélien
dc.contributor.authorKleefstra, Tjitske
dc.contributor.authorVerloes, Alain
dc.contributor.authorVissers, Lisenka E L M
dc.contributor.authorPosada De la Paz, Manuel
dc.identifier.citationEur J Hum Genet. 2021 Sep;29(9):1359-1368.es_ES
dc.descriptionCorrection: A MT-TL1 variant identified by whole exome sequencing in an individual with intellectual disability, epilepsy, and spastic tetraparesis. Eur J Hum Genet. 2021 Sep;29(9):1470-1471. doi: 10.1038/s41431-021-00937-3.es_ES
dc.description.abstractThe 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.es_ES
dc.description.sponsorshipThis work was financially supported by Aspasia grants of the Dutch Research Council (015.014.036 to TK and 015.014.066 to LELMV), the European Research Council (ERC to RH), the Well come Investigator Award (109915/Z/15/Z to RH), the Medical Research Council UK (MR/N025431/1 to RH), the Newton Fund (MR/N027302/1 to RH), the Lily Foundation (RH), and the Evelyn Trust (RH). The Solve-RD project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 779257.es_ES
dc.publisherSpringer es_ES
dc.relation.isversionofPublisher's versiones_ES
dc.subject.meshEpilepsy es_ES
dc.subject.meshHumans es_ES
dc.subject.meshIntellectual Disability es_ES
dc.subject.meshMale es_ES
dc.subject.meshMutation es_ES
dc.subject.meshQuadriplegia es_ES
dc.subject.meshRNA, Transfer, Leu es_ES
dc.subject.meshWhole Exome Sequencing es_ES
dc.subject.meshYoung Adult es_ES
dc.titleA MT-TL1 variant identified by whole exome sequencing in an individual with intellectual disability, epilepsy, and spastic tetraparesises_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.contributor.funderDutch Research Council (Holanda) es_ES
dc.contributor.funderEuropean Research Council es_ES
dc.contributor.funderMedical Research Council (Reino Unido) es_ES
dc.contributor.funderNewton Fundes_ES
dc.contributor.funderLily Foundation es_ES
dc.contributor.funderUnión Europea. Comisión Europea. H2020 es_ES
dc.identifier.journalEuropean journal of human genetics : EJHGes_ES
dc.repisalud.centroISCIII::Instituto de Investigación de Enfermedades Rarases_ES

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Atribución-NoComercial-CompartirIgual 4.0 Internacional
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