Elkhateeb, N. orcid.org/0000-0002-3076-3178, Crookes, R., Spiller, M. et al. (68 more authors) (2025) Expanding the phenotype and genotype spectrum of TAOK1 neurodevelopmental disorder and delineating TAOK2 neurodevelopmental disorder. Genetics in Medicine, 27 (3). 101348. ISSN 1098-3600
Abstract
PURPOSE: The TAOK proteins are a group of serine/threonine-protein kinases involved in signalling pathways, cytoskeleton regulation, and neuronal development. TAOK1 variants are associated with a neurodevelopmental disorder (NDD) characterized by distinctive facial features, hypotonia and feeding difficulties. TAOK2 variants have been reported to be associated with autism and early-onset obesity. However, a distinct TAOK2-NDD has not yet been delineated.
METHODS: We retrospectively studied the clinical and genetic data of individuals recruited from several centres with TAOK1 and TAOK2 variants that were detected through exome and genome sequencing.
RESULTS: We report 50 individuals with TAOK1 variants with associated phenotypes including neurodevelopmental abnormalities (100%), macrocephaly (83%) and hypotonia (58%). We report male genital anomalies and hypoglycaemia as novel phenotypes. Thirty-seven unique TAOK1 variants were identified. Most of the missense variants clustered in the protein kinase domain at residues that are intolerant to missense variation. We report ten patients with TAOK2 variants with associated phenotypes including neurodevelopmental abnormalities (100%), macrocephaly (75%), autism (75%), and obesity (70%).
CONCLUSION: We describe the largest cohort of TAOK1-NDD to date, expanding its phenotype and genotype spectrum with thirty novel variants. We delineate the phenotype of a novel TAOK2-NDD associated with neurodevelopmental abnormalities, autism, macrocephaly, and obesity.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 The Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | MAP3K enzymes; TAOK1; TAOK2; Thousand and one kinase family; neurodevelopmental disorder |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine and Population Health |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 07 Jan 2025 15:27 |
Last Modified: | 11 Feb 2025 08:49 |
Status: | Published |
Publisher: | Elsevier BV |
Refereed: | Yes |
Identification Number: | 10.1016/j.gim.2024.101348 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:221338 |