O24: Heterozygous de novo variants in CDKL1 and CDKL2 cause neuroregressive phenotypes in Human and Drosophila and are dominant negative alleles
The CDKL (cyclin-dependent kinase-like) genes are a conserved family of protein kinases, consisting of CDKL1-5. The genes are expressed in a variety of tissues, including the nervous system. CDKL5 is the only member of the CDKL family linked to a Mendelian disease and causes developmental and epileptic encephalopathy type 2 (DEE2). Here, we report that de novo variants in CDKL1 or CDKL2 contribute to neurodevelopmental phenotypes in both humans and Drosophila melanogaster. We utilized Drosophila as a model organism to investigate the pathogenicity of the variants and to study the underlying mechanisms of these variants.
Authors
- Oguz Kanca (ORCID: https://orcid.org/0000-0001-5438-0879)
- Güney Bademci (ORCID: https://orcid.org/0000-0002-4052-8833)
- Hugo J. Bellen (ORCID: https://orcid.org/0000-0001-5992-5989)
- Jonathan Andrews (ORCID: https://orcid.org/0000-0002-1257-9342)
- Stephanie Bivona (ORCID: https://orcid.org/0009-0001-9824-0306)
- Shane McKee (ORCID: https://orcid.org/0000-0002-1772-0106)
- Wendy Chung
- Mustafa Tekin (ORCID: https://orcid.org/0000-0002-3525-7960)
- Daniel F. Eberl (ORCID: https://orcid.org/0000-0001-9982-9895)
- Nicholas A. Borja (ORCID: https://orcid.org/0000-0002-9199-9096)
- Shinya Yamamoto
- Ali Hosseini Bereshneh (ORCID: https://orcid.org/0000-0003-1602-3605)
- Michael F. Wangler (ORCID: https://orcid.org/0000-0001-5245-5910)
Institutions
- University of Iowa (US)
- Boston Children's Hospital (US)
- Harvard University (US)
- University of Ulster (GB)
- Belfast City Hospital (GB)
- Neurological Research Institute (US)
- Dr. John T. Macdonald Foundation (US)
Publication Details
- Journal
- Genetics in Medicine Open
- Published
- 2025-01-01
- DOI
- https://doi.org/10.1016/j.gimo.2025.102100
- Primary Topic
- Genetics and Neurodevelopmental Disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00