Severe neurodevelopmental disease caused by a homozygous TLK2 variant

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, o...

Descripción completa

Detalles Bibliográficos
Autores: Topf, Ana, Oktay, Yavuz, Balaraju, Sunitha, Yilmaz, Elmasnur, Sonmezler, Ece, Yis, Uluc, Laurie, Steven, 1973-, Thompson, Rachel, Roos, Andreas, MacArthur, Daniel G., Yaramis, Ahmet, Güngör, Serdal, Lochmüller, Hanns, Hiz, Semra, Horvath, Rita
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/43952
Acceso en línea:http://hdl.handle.net/10230/43952
http://dx.doi.org/10.1038/s41431-019-0519-x
Access Level:acceso abierto
Palabra clave:Trastorns del neurodesenvolupament
Genètica
Proteïnes
id ES_eeb493e3b9fde779518ffa17df2ec752
oai_identifier_str oai:repositori.upf.edu:10230/43952
network_acronym_str ES
network_name_str España
repository_id_str
spelling Severe neurodevelopmental disease caused by a homozygous TLK2 variantTopf, AnaOktay, YavuzBalaraju, SunithaYilmaz, ElmasnurSonmezler, EceYis, UlucLaurie, Steven, 1973-Thompson, RachelRoos, AndreasMacArthur, Daniel G.Yaramis, AhmetGüngör, SerdalLochmüller, HannsHiz, SemraHorvath, RitaTrastorns del neurodesenvolupamentGenèticaProteïnesA 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.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)Springer202020202020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/43952http://dx.doi.org/10.1038/s41431-019-0519-xreponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésEuropean Journal of Human Genetics. 2020 Mar; 28(3): 383-7info:eu-repo/grantAgreement/EC/FP7/309548info:eu-repo/grantAgreement/EC/FP7/305444This 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 madehttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/439522026-06-12T07:21:37Z
dc.title.none.fl_str_mv Severe neurodevelopmental disease caused by a homozygous TLK2 variant
title Severe neurodevelopmental disease caused by a homozygous TLK2 variant
spellingShingle Severe neurodevelopmental disease caused by a homozygous TLK2 variant
Topf, Ana
Trastorns del neurodesenvolupament
Genètica
Proteïnes
title_short Severe neurodevelopmental disease caused by a homozygous TLK2 variant
title_full Severe neurodevelopmental disease caused by a homozygous TLK2 variant
title_fullStr Severe neurodevelopmental disease caused by a homozygous TLK2 variant
title_full_unstemmed Severe neurodevelopmental disease caused by a homozygous TLK2 variant
title_sort Severe neurodevelopmental disease caused by a homozygous TLK2 variant
dc.creator.none.fl_str_mv Topf, Ana
Oktay, Yavuz
Balaraju, Sunitha
Yilmaz, Elmasnur
Sonmezler, Ece
Yis, Uluc
Laurie, Steven, 1973-
Thompson, Rachel
Roos, Andreas
MacArthur, Daniel G.
Yaramis, Ahmet
Güngör, Serdal
Lochmüller, Hanns
Hiz, Semra
Horvath, Rita
author Topf, Ana
author_facet Topf, Ana
Oktay, Yavuz
Balaraju, Sunitha
Yilmaz, Elmasnur
Sonmezler, Ece
Yis, Uluc
Laurie, Steven, 1973-
Thompson, Rachel
Roos, Andreas
MacArthur, Daniel G.
Yaramis, Ahmet
Güngör, Serdal
Lochmüller, Hanns
Hiz, Semra
Horvath, Rita
author_role author
author2 Oktay, Yavuz
Balaraju, Sunitha
Yilmaz, Elmasnur
Sonmezler, Ece
Yis, Uluc
Laurie, Steven, 1973-
Thompson, Rachel
Roos, Andreas
MacArthur, Daniel G.
Yaramis, Ahmet
Güngör, Serdal
Lochmüller, Hanns
Hiz, Semra
Horvath, Rita
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Trastorns del neurodesenvolupament
Genètica
Proteïnes
topic Trastorns del neurodesenvolupament
Genètica
Proteïnes
description 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.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/43952
http://dx.doi.org/10.1038/s41431-019-0519-x
url http://hdl.handle.net/10230/43952
http://dx.doi.org/10.1038/s41431-019-0519-x
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv European Journal of Human Genetics. 2020 Mar; 28(3): 383-7
info:eu-repo/grantAgreement/EC/FP7/309548
info:eu-repo/grantAgreement/EC/FP7/305444
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869423745944256512
score 15,812455

Similares en LA Referencia