CDKL5 Variants: Improving our understanding of a rare neurological disorder

Dr Ralph Hector, a researcher fellow in the lab of Dr Stuart Cobb has recently had a paper published in the journal Neurology Genetics on improving our understanding of the rare neurological disorder, CDKL5.

This is a study of all the genetic variants we see in the CDKL5 gene, in patients with CDKL5 deficiency and in the general population. The study, a collaboration with clinicians in Europe, USA and Australia, analysed data from recent large-scale studies in which thousands of people in the general population had their DNA and RNA sequenced. We compared the data from these populations with patients with mutations in CDKL5 to gain insights into which parts of the gene (and protein) are important for CDKL5 function, and how best to target genetic therapies. Certain types of variants (missense variants, where a single amino acid is changed in the CDKL5 protein) cluster in the catalytic domain of CDKL5. This means that the catalytic domain is almost certainly the most important domain in CDKL5 in terms of its function. We also found more evidence that variants in the last three exons of CDKL5 (exons are the building blocks of the gene) are unlikely to be disease-causing, adding weight to a 2014 study. This tells us something about how important the different protein isoforms are to the pathogenicity of CDKL5 (isoforms are the different versions of CDKL5 protein produced in the cell). This information is helping to inform our lab and other labs about how best to develop therapies for CDKL5 deficiency.

Read the full paper in Neurology Genetics Here

A blog written by the author for CDKL5 UK

Dr Stuart Cobb’s website

This study was funded by CDKL5 UK