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Severe neurodevelopmental disease caused by a homozygous TLK2 variant

Lookup NU author(s): Dr Ana TopfORCiD, Sunitha Balaraju, Rachel ThompsonORCiD, Dr Andreas Roos, Professor Hanns Lochmuller, Professor Rita HorvathORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2019, The Author(s).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.

Publication metadata

Author(s): Topf A, Oktay Y, Balaraju S, Yilmaz E, Sonmezler E, Yis U, Laurie S, Thompson R, Roos A, MacArthur DG, Yaramis A, Gungor S, Lochmuller H, Hiz S, Horvath R

Publication type: Article

Publication status: Published

Journal: European Journal of Human Genetics

Year: 2020

Volume: 28

Pages: 383–387

Print publication date: 01/03/2020

Online publication date: 26/09/2019

Acceptance date: 02/04/2019

Date deposited: 04/11/2019

ISSN (print): 1018-4813

ISSN (electronic): 1476-5438

Publisher: Nature Publishing Group


DOI: 10.1038/s41431-019-0519-x

PubMed id: 31558842


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Funder referenceFunder name
109915/Z/15/ZWellcome Trust
201064/Z/16/ZWellcome Trust
203105/Z/16/ZWellcome Trust
MR/N027302/1Medical Research Council (MRC)
MR/N025431/1Medical Research Council (MRC)
UMI HG008900