Severe neurodevelopmental disease caused by a homozygous TLK2 variant

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• dc.contributor.author Topf, Ana
• dc.contributor.author Oktay, Yavuz
• dc.contributor.author Balaraju, Sunitha
• dc.contributor.author Yilmaz, Elmasnur
• dc.contributor.author Sonmezler, Ece
• dc.contributor.author Yis, Uluc
• dc.contributor.author Laurie, Steven, 1973-
• dc.contributor.author Thompson, Rachel
• dc.contributor.author Roos, Andreas
• dc.contributor.author MacArthur, Daniel G.
• dc.contributor.author Yaramis, Ahmet
• dc.contributor.author Güngör, Serdal
• dc.contributor.author Lochmüller, Hanns
• dc.contributor.author Hiz, Semra
• dc.contributor.author Horvath, Rita
• dc.date.accessioned 2020-03-19T10:08:19Z
• dc.date.available 2020-03-19T10:08:19Z
• dc.date.issued 2020
• dc.description.abstract A distinct neurodevelopmental phenotype characterised mainly by mild motor and language delay and facial dysmorphism, caused by heterozygous de novo or dominant variants in the TLK2 gene has recently been described. All cases reported carried either truncating variants located throughout the gene, or missense changes principally located at the C-terminal end of the protein mostly resulting in haploinsufficiency of TLK2. Through whole exome sequencing, we identified a homozygous missense variant in TLK2 in a patient showing more severe symptoms than those previously described, including cerebellar vermis hypoplasia and West syndrome. Both parents are heterozygous for the variant and clinically unaffected highlighting that recessive variants in TLK2 can also be disease causing and may act through a different pathomechanism.
• dc.description.sponsorship The project is supported by TUBITAK (The Scientific and Technological Research Council of Turkey) Project No. 216S771. RH is a Wellcome Trust Investigator (109915/Z/15/Z), who receives support from the Wellcome Centre for Mitochondrial Research (203105/Z/16/Z), Medical Research Council (UK) (MR/N025431/1), the European Research Council (309548), the Wellcome Trust Pathfinder Scheme (201064/Z/16/Z) and the Newton Fund (UK/Turkey, MR/N027302/1). The Broad Centre for Mendelian Genomics (UM1 HG008900) is funded by the National Human Genome Research Institute with supplemental funding provided by the National Heart, Lung, and Blood Institute under the Trans-Omics for Precision Medicine (TOPMed) programme and the National Eye Institute. Data were analysed using the RD-Connect Genome-Phenome Analysis platform developed under FP7/2007-2013 funded project (grant agreement no. 305444)
• dc.format.mimetype application/pdf
• dc.identifier.citation Töpf A, Oktay Y, Balaraju S, Yilmaz E, Sonmezler E, Yis U et al. Severe neurodevelopmental disease caused by a homozygous TLK2 variant. Eur J Hum Genet. 2020 Mar; 28(3): 383-387. DOI: 10.1038/s41431-019-0519-x
• dc.identifier.doi http://dx.doi.org/10.1038/s41431-019-0519-x
• dc.identifier.issn 1018-4813
• dc.identifier.uri http://hdl.handle.net/10230/43952
• dc.language.iso eng
• dc.publisher Springer
• dc.relation.ispartof European Journal of Human Genetics. 2020 Mar; 28(3): 383-7
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/309548
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/305444
• dc.rights This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.other Trastorns del neurodesenvolupament
• dc.subject.other Genètica
• dc.subject.other Proteïnes
• dc.title Severe neurodevelopmental disease caused by a homozygous TLK2 variant
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion