Show simple item record

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 JH
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
dc.contributor.authorTrimouille, Aurélien
dc.contributor.authorKleefstra, Tjitske
dc.contributor.authorVerloes, Alain
dc.contributor.authorVissers, Lisenka ELM
dc.date.accessioned2021-09-24T15:32:45Z
dc.date.available2021-09-24T15:32:45Z
dc.date.issued2021-09
dc.date.submitted2020-10-13
dc.identifier.issn1018-4813
dc.identifier.others41431-021-00900-2
dc.identifier.other900
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/328490
dc.descriptionFunder: The Solve-RD project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 779257
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.
dc.languageen
dc.publisherSpringer Science and Business Media LLC
dc.subjectBrief Communication
dc.subject/692/308/2056
dc.subject/692/699/375
dc.subject/692/699/375/366
dc.subject/692/308/575
dc.subject/45/23
dc.subjectbrief-communication
dc.titleA MT-TL1 variant identified by whole exome sequencing in an individual with intellectual disability, epilepsy, and spastic tetraparesis.
dc.typeArticle
dc.date.updated2021-09-24T15:32:45Z
prism.endingPage1368
prism.issueIdentifier9
prism.publicationNameEur J Hum Genet
prism.startingPage1359
prism.volume29
dc.identifier.doi10.17863/CAM.75938
dcterms.dateAccepted2021-04-15
rioxxterms.versionofrecord10.1038/s41431-021-00900-2
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidOckeloen, Charlotte W [0000-0003-0329-1520]
dc.contributor.orcidHorvath, Rita [0000-0002-9841-170X]
dc.contributor.orcidRodenburg, Richard J [0000-0001-5227-3527]
dc.contributor.orcidGilissen, Christian [0000-0003-1693-9699]
dc.contributor.orcidSteyaert, Wouter [0000-0001-8393-0788]
dc.contributor.orcidTrimouille, Aurélien [0000-0002-3457-5684]
dc.contributor.orcidVerloes, Alain [0000-0003-4819-0264]
dc.contributor.orcidVissers, Lisenka ELM [0000-0001-6470-5497]
dc.identifier.eissn1476-5438
pubs.funder-project-idWellcome Trust (109915_A_15_Z)
pubs.funder-project-idMedical Research Council (MR/N025431/2)
pubs.funder-project-idMRC (MR/V009346/1)
cam.issuedOnline2021-06-01


Files in this item

Thumbnail
Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record