Woods, E., Spiller, M. and Balasubramanian, M. orcid.org/0000-0003-1488-3695 (2022) Report of two children with global developmental delay in association with de novo TLK2 variant and literature review. American Journal of Medical Genetics Part A, 188 (3). pp. 931-940. ISSN 1552-4825
Abstract
We describe clinical details, including novel findings, of two further children with the newly defined TLK2-related disorder. One patient was recruited to the Deciphering Developmental Delay (DDD) Study to identify underlying etiology of global developmental delay. The other was detected on whole-exome sequencing as part of second line investigations following normal microarray. Both patients were found to have de novo heterozygous pathogenic TLK2 variants. A novel c.6del p.(Glu3Lysfs*) loss-of-function frameshift variant was found in Patient 1. A c.1121+1G>A splice-donor variant was detected in Patient 2. TLK2-related neurodevelopmental disorder is a specific syndrome that has been recently described. Global developmental delay, behavioral problems, gastrointestinal disorders, and typical facial dysmorphism are common features. Neuropsychiatric disorders, ophthalmic, musculoskeletal and cranial abnormalities, as well as short stature, have also all been described. The novel findings we describe include sleep disturbance, nondifferentiation of lateral semi-circular canals (where asymmetric semi-circular canals were a feature in the previous cohort), vesico-ureteric reflux, and bilateral periauricular skin tags. Here, we report a novel TLK2 variant and previously undescribed features of TLK2-related disorder, to expand the clinical phenotype and provide further genotype–phenotype correlation.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 Wiley Periodicals LLC. This is an author-produced version of a paper subsequently published in American Journal of Medical Genetics Part A. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | autism spectrum disorder; neurodevelopment; TLK2 |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 26 Apr 2022 12:31 |
Last Modified: | 25 Nov 2022 01:13 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1002/ajmg.a.62580 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:185793 |