Oguz Kanca

Thank you very much for the kind words, Tim. Just a small correction, it was the GDP and DRSC that got the award.

De novo variants in CDKL1 and CDKL2 are associated with neurodevelopmental symptoms This study identifies de novo variants in CDKL1 and CDKL2 in individuals with neurodevelopmental symptoms and seizures. Functional analysis in fruit flies provides compelling evidence that these varia...

📣New from @okanca.bsky.social & co
📄De novo variants in CDKL1 and CDKL2 are associated with neurodevelopmental symptoms
🧬🪰🧠

The project was done by a talented postdoc in our lab Ali Bereshneh. The paper can be reached following the link below:
authors.elsevier.com/a/1km46geXDylR

We are grateful to families and individuals who participated in the study and our clinical collaborators for an excellent collaboration. We are also grateful for our fly collaborators Jonathan Andrews and Daniel Eberl.

We noticed that when we co-express the variant CDKL1 or 2 together with reference CDKL5 in Cdkl mutant background,(or CDKL1 or 2) the rescue ability of reference genes was impaired. This indicates that the variants we identified act in a dominant negative manner.

All the individuals in our cohort are de novo heterozygous individuals, suggesting the variants we tested were unlikely to be loss of function alleles. We tested whether variants in CDKL1 or 2 can impinge on the function of reference CDKL genes.

Variants in CDKL1 and CDKL2 either failed to rescue the observed phenotypes or rescued partially. CDKL genes with the exception of CDKL5 are tolerant to variation, with many individuals in control populations with one copy loss of CDKL1 or 2.

We broaden our search to paralogs of CDKL2 to find variants that may be associated with Mendelian Diseases. We identified two variants in CDKL1 presenting with developmental delay in publicly available Deciphering Developmental Delay and GeneDx consortia that we included in our analysis.

Interestingly, loss of Cdkl caused semi lethality, heat induced seizures and climbing defects. These phenotypes could be rescued by expressing the reference UAS human cDNAs of CDKL1, CDKL2, CDKL4 and CDKL5.

To our surprise, Cdkl was very sparsely expressed in the central nervous system but we noticed Cdkl expression in every sensory neuron we analyzed (with the exception of photoreceptors). Below is our contribution to fluorescent Friday

We generated a versatile allele of Cdkl, Cdkll-T2AGAL4 that allow us to determine the expression pattern of the gene and loss of function phenotypes associated with the loss of the gene. More details about the methodology and similar alleles can be found in flypush.research.bcm.edu/pscreen/crim...

We used fruit fly model to study the impact of the identified variants. Drosophila has a single gene CG7236 (that we propose to rename Cdkl) which is orthologous to all 5 CDKL family of genes.

Through gene matching efforts we connected with other clinical collaborators from Harvard Medical School and Belfast City Hospital who identified individuals with CDKL2 variants presenting with neuorodevelopmental symptoms partially overlapping with CDD symptoms.

Variants in CDKL5 cause CDKL5 Deficiency Disorder (CDD), which is a rare disease with severe symptoms. Individuals with CDKL5 Deficiency disorder typically show symptoms including early onset epilepsy and developmental delay.

It all started with our clinical collaborators from the Undiagnosed Diseases Network who identified an individual with a de novo variant in CDKL2 gene. CDKL2 is a member of Cyclin Dependent Kinase Like gene family. The only CDKL family member associated with a Mendelian disease was CDKL5.

New CDKL genes linked to neurodevelopmental disorders CDKL5, one of the five members of the CDKL family of genes, is important for proper neurodevelopment and associated with seizures. However, the role the...

We are excited to share our latest paper published today linking specific variants in CDKL2 and CDKL1 to a novel neurodevelopmental disorder.
www.bcm.edu/news/new-cdk...

Look what I made! 🦋 With help from Scholar Goggler scholargoggler.com made by @morinryan.bsky.social.
Thanks @axelvisel.bsky.social for inspiration.

Admittedly, flies are not as boopworthy but it reminded me of our cover from 2014.

Hello Bsky folks - here is a paper that we published earlier this year - great collaboration with the Bellen lab, Hyung-lok Chung, @okanca.bsky.social and others. Have a look if you're interested in Cdk8/19, mitochondria, Parkinsonism and Drosophila!

Thank you Filip. And thanks for making the starter pack.

Could you please add me too?

All these awesome starter packs are a great way to find folks to invite to conferences or seminars! I've met so many new people in the last few days 🪰🐸🪱🐭🐠
Check out the Animal models of disease one I made!
go.bsky.app/MhUwjSx

I think when you swipe left you go from discovery mode to following mode where you only see the posts from those you follow. Does that help?

I thought we could use a Drosophila starter pack, please let me know if you’d like to be added. (I think there is also a more general insect list out there somewhere that i cant find rn..) go.bsky.app/JGggkH3

I’d love to be added if possible. Thank you for the starter list

I really enjoyed cooking for geeks by Jeff Potter

I can recommend Citizen sleeper too as a Disco inspired game. I started playing it recently and it’s quite a nice game