Severe neurodevelopmental disease caused by a homozygous TLK2 variant.

TitleSevere neurodevelopmental disease caused by a homozygous TLK2 variant.
Publication TypeJournal Article
Year of Publication2020
AuthorsTopf, A, Oktay, Y, Balaraju, S, Yilmaz, E, Sonmezler, E, Yis, U, Laurie, S, Thompson, R, Roos, A, MacArthur, DG, Yaramis, A, Güngör, S, Lochmüller, H, Hiz, S, Horvath, R
JournalEur J Hum Genet
Volume28
Issue3
Pagination383-387
Date Published2020 Mar
ISSN1476-5438
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.

DOI10.1038/s41431-019-0519-x
Alternate JournalEur. J. Hum. Genet.
PubMed ID31558842
PubMed Central IDPMC7028915
Grant ListUM1 HG008900 / HG / NHGRI NIH HHS / United States
201064 / WT / Wellcome Trust / United Kingdom
203105 / WT / Wellcome Trust / United Kingdom
/ WT / Wellcome Trust / United Kingdom
109915 / WT / Wellcome Trust / United Kingdom