I absolutely love this figure in a second paper led by Adam Jackson, @alexblakes.bsky.social, and Sid Banka (www.medrxiv.org/content/10.1...) of RNU gene diagnoses in @genomicsengland.bsky.social 100k genomes project.

(1) showing just how many new diagnoses are found across these genes ❤️

2/3

The biology here is fascinating too. Really nice to see the clustering of compound het / homozygous variants in the Sm site in your cohort for example.

Congratulations to you and the whole team on this really beautiful work. This is a really important discovery for patients and families affected by rare conditions.

This is ... just brilliant. Another ncRNA gene involved in rare developmental diseases, and these are a meaningful number of new cases - also interesting the dominance/linear/recessive differences

After our study on RNU4-2 and RNU5B-1 published in May (Nava et al, Nature Genetics 2025), I am excited to share our new preprint reporting dominant and recessive variants in RNU2-2 as a frequent cause of developmental and epileptic encephalopathy (DEE).

📄 www.medrxiv.org/content/10.1...

(2) but even cooler is the flip of frequency between dominant and recessive forms in RNU4-2 and RNU2-2, driven by different signatures of mutation and selection - variants across RNU2-2 tend to be more common, driving a higher comp het frequency.

We have a lot to learn from these genes yet!!! 🧬🤓

While I was taking a holiday last week, 2 super exciting preprints dropped, adding to another posted 6 days prior.

These papers describe a remarkable role for *recessive* variants in *RNU2-2* causing developmental and epileptic encephalopathy

🧵 by the amazing @christeldepienne.bsky.social 👇

1/3

Congratulations @alextremophile.bsky.social, tremendous to see this online! :)

I am super proud to present our new manuscript “Using SpliceAI to triage splice-altering variants in 7,220 individuals with rare conditions highlights limitations of the precomputed scores”
www.medrxiv.org/content/10.1...

Love when you can build a paper out of a personal bugbear! tl;dr the precomputed SpliceAI scores are great, but proceed with caution!

Very exciting to have access to "Our Future Health" data and begin understanding what is available and how to access it

Many thanks to the volunteers so far. Still a long way to go - consider signing up if you haven't already!

This is a greater primer on the aims www.nature.com/articles/s41...

3/3 I am thrilled to be part of a study establishing the clinical phenotypes of NDD associated with recessive variants in RNU4-2. Thank you to @rociorius.bsky.social, @alexblakes.bsky.social, @cassimons.bsky.social and @nickywhiffin.bsky.social for leading this work! More details: lnkd.in/eTJ5Rapt

1st Bluesky post with recent updates:
1/3 It was incredible to attend and speak at the ReNU Hope Conference in Long Island, NY. This was the first time I met the families and the ReNU warriors, sharing many touching stories. I hope to continue advocacy in China where few are currently diagnosed.

Nuevo diagnóstico ligado a #RNU4-2 🧬: variantes bialélicas causan un #TND recesivo con cambios característicos en sustancia blanca en RM 👉 hay que considerar este gen no codificante en la búsqueda/diagnóstico.
tinyurl.com/3j9r56s8
La historia completa la cuenta @alexblakes.bsky.social aqui 🧵👇

New preprint! The outcome of a wonderful collaboration with @nickywhiffin.bsky.social’s team to define a new recessive syndrome associated with inherited variants in RNU4-2, the non-protein-coding gene that keeps on giving.

This whole thread describes how 18 months of work on this tiny piece of genome identified 2/3 new syndromes. it’s a very compelling clinical genetics story!

Our latest research is out today on ‪@medrxivpreprint.bsky.social:

www.medrxiv.org/content/10.1...

Saturation genome editing of BRCA1 across cell types accurately resolves cancer risk.

Led by the amazing Phoebe Dace. This one’s packed full of data, so check out the paper. Quick highlights… 🧵 1/n

Isn't genetics cool???

Within only 145 nucleotides(!) of a non-coding RNA (RNU4-2) - different variants in distinct regions / structures cause three distinct disorders!!! (all discovered within the last 18 months)

🤯🤓🧬❤️

Look at the insane speed of discovery around this snippet of DNA. Sometimes the machine of science is amazing. 🤩

An awesome piece of work by @alexblakes.bsky.social, @rociorius.bsky.social, @nickywhiffin.bsky.social and team!

I am super excited to see more emerging from this tiny, but mighty gene, and am overjoyed at the implications this has for the rare disorders community ❤️

We recently performed SGE of RNU4-2 and identified functionally impactful variants underlying a new recessive disease. Today, the team led by @rociorius.bsky.social @alexblakes.bsky.social @cassimons.bsky.social & @nickywhiffin.bsky.social provide in-depth analysis of its clinical presentation. 🧵⬇️

🚨 New preprint led by amazing duo @rociorius.bsky.social and @alexblakes.bsky.social in collaboration with @cassimons.bsky.social, @dgmacarthur.bsky.social and many other amazing folks! ❤️

We describe the clinical phenotype of a recessive NDD associated with biallelic variants in RNU4-2 🧬

See 🧵👇

I learned so much from this work and I hope that and discoveries like this can make a real difference to the lives of people living with #RareConditions. Please do share! 😊
www.medrxiv.org/content/10.1...

Thanks also to the institutions whose incredible resources and platforms have made this work possible, including @ukbiobank.bsky.social, @genomicsengland.bsky.social, @manchester.ac.uk, @ox.ac.uk, as well as our funders including @wellcometrust.bsky.social.