TAOK-related neurodevelopmental disorders: Natural History Study
Research type
Research Study
Full title
TAOK-related neurodevelopmental disorders: Natural History Study
IRAS ID
348972
Contact name
Meena Balasubramanian
Contact email
Sponsor organisation
Sheffield Children's NHS Foundation Trust
Duration of Study in the UK
5 years, 0 months, 2 days
Research summary
Background: The Thousand and One kinase family (TAOKs) include three proteins TAOK1, TAOK2, and TAOK3. Disease-causing gene changes in each of the three genes are associated with neurodevelopmental disorders (NDD) with distinct yet overlapping features. TAOK1-related NDD is associated with developmental and learning problems, similar facial features, hypotonia, feeding, and growth difficulties. TAOK2-related NDD is newly described and linked to developmental and learning difficulties, macrocephaly (large head size), and obesity. There is growing evidence that TAOK3 gene changes are associated with developmental problems, microcephaly (small head size), and seizures. We aim to develop a natural history study to collect long-term information on individuals with TAOK-related NDDs, aiming to improve the evaluation of the TAOK-related NDDs in terms of individualised patient-centred care.
Approach: We will be collecting clinical and genetic data on all participants. With consent, we will obtain blood and skin biopsy samples from the affected individuals (this is optional), to study genetic changes in more detail. These samples may potentially be used to transform patient cells into firstly stem and then nerve cells (neurons), to characterise their properties using cutting-edge genomics technologies.
Outcomes: We will describe how TAOK-related NDDs change over time, and how different genetic changes relate to specific clinical features. This will help us identify common health challenges and provide clearer guidance for families and clinicians. The blood and skin samples will optionally be collected to create a resource that can be used in future functional studies and facilitate future collaborative projects..
Impact: We currently have the largest cohort of TAOK-related disorders in the UK and internationally; with data from over 80 families that have been or are being published, therefore the project proposal is ideally located for immediate benefit. This work is timely, forming a basis for future functional studies that are a stepping stone for potential research into future therapies.
REC name
Yorkshire & The Humber - Leeds West Research Ethics Committee
REC reference
25/YH/0257
Date of REC Opinion
9 Apr 2026
REC opinion
Further Information Favourable Opinion