Journal article
CDKL5 deficiency disorder: molecular insights and mechanisms of pathogenicity to fast-track therapeutic development
NJ Van Bergen, S Massey, A Quigley, B Rollo, AR Harris, RMI Kapsa, J Christodoulou
Biochemical Society Transactions | Published : 2022
DOI: 10.1042/BST20220791
Open access
Abstract
CDKL5 deficiency disorder (CDD) is an X-linked brain disorder of young children and is caused by pathogenic variants in the cyclin-dependent kinase-like 5 (CDKL5) gene. Individuals with CDD suffer infantile onset, drug-resistant seizures, severe neurodevelopmental impairment and profound lifelong disability. The CDKL5 protein is a kinase that regulates key phosphorylation events vital to the development of the complex neuronal network of the brain. Pathogenic variants identified in patients may either result in loss of CDKL5 catalytic activity or are hypomorphic leading to partial loss of function. Whilst the progressive nature of CDD provides an excellent opportunity for disease interventio..
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Awarded by Royal Children's Hospital Foundation
Funding Acknowledgements
The research conducted at the Murdoch Children's Research Institute was supported by the Victorian Government `s Operational Infrastructure Support Program. Funding to N.J.V.B. was provided by the Foundation for Children Project Grant (2018-16), Murdoch Children's Research Institute Strategic Pilot Project in Stem Cell and Genomic Medicine Research Grant, Million Dollar Bike Ride pilot grant from the Orphan Disease Center of the University of Pennsylvania (MDBR-20-106-CDKL5), the CDKL5 Forum Junior Fellowship from the Loulou Foundation and the Medical Research Future Funds (MRFF) Stem Cell Therapies Mission (MRF2007465). A.Q. is funded by an RMIT Vice Chancellor's Senior Fellowship and a St Vincent's Hospital Australia Endowment Grant. B.R. is supported by the Medical Research Future Funds (MRFF) Stem Cell Therapies Mission (APP1201781). The Chair in Genomic Medicine awarded to J.C. is generously supported by The Royal Children's Hospital Foundation. NHMRC Project 2002723 (R.M.I.K.) provides support for some of the aspects for this project.