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Christel Depienne @christeldepienne.bsky.social · Sep 8

Congrats to you as well!
Amazing to see how different approaches led to outcomes that are both similar and wonderfully complementary 😊

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Reposted by Christel Depienne

Nicky Whiffin @nickywhiffin.bsky.social · Sep 8

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 👇

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Christel Depienne @christeldepienne.bsky.social · Sep 5

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...

Systematic analysis of snRNA genes reveals frequent RNU2-2 variants in dominant and recessive developmental and epileptic encephalopathies

Variants in spliceosomal small nuclear RNA (snRNA) genes RNU4-2 (ReNU syndrome), RNU5B-1 , and RNU2-2 have recently been linked to dominant neurodevelopmental disorders (NDDs), revealing a major, prev...

www.medrxiv.org

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Christel Depienne @christeldepienne.bsky.social · Sep 5

Link to
Our previous article: www.nature.com/articles/s41...

Dominant variants in major spliceosome U4 and U5 small nuclear RNA genes cause neurodevelopmental disorders through splicing disruption - Nature Genetics

Analysis of snRNA genes in individuals with rare disorders identifies de novo and recurrent variants in RNU5B-1 and RNU5A-1, in addition to previously unreported cases with pathogenic or likely pathog...

www.nature.com

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Christel Depienne @christeldepienne.bsky.social · Sep 5

Elsa Leitao
Amandine Santini
Benjamin Cogne
Myriam Essie
Clément Charenton
Camille Charbonnier
Gaetan Lesca
Caroline Nava
@hcmefford.bsky.social @nickywhiffin.bsky.social
@cwlaflamme.bsky.social
And many many others

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Christel Depienne @christeldepienne.bsky.social · Sep 5

This study brought together >200 collaborators worldwide and would not have been possible without the contribution of the Plan France Médecine Génomique (PFMG). 🙏

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Christel Depienne @christeldepienne.bsky.social · Sep 5

Importantly, these findings are independently supported by two other preprints, including one posted the exact same day:
📄 www.medrxiv.org/content/10.1...

Biallelic variants in RNU2-2 cause a remarkably frequent developmental epileptic encephalopathy

Neurodevelopmental disorders (NDDs) affect 2-4% of the population, are predominantly genetic, and remain unsolved in ~50% of individuals. We show that rare biallelic variants in RNU2-2 are enriched an...

www.medrxiv.org

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Christel Depienne @christeldepienne.bsky.social · Sep 5

Transcriptomic and DNA methylation analyses showed subtle, variant-specific effects on splicing and episignatures.
Our results support a continuum between dominant and recessive disorders and establish RNU2-2 DEE as nearly as frequent as ReNU syndrome (RNU4-2),

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Christel Depienne @christeldepienne.bsky.social · Sep 5

Remarkably, recessive RNU2-2 DEE is at least twice as common as the dominant form.
It often arises from a de novo variant in trans with an inherited allele, reflecting the high mutability of snRNA genes.

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Christel Depienne @christeldepienne.bsky.social · Sep 5

We analyzed 200 potentially functional spliceosomal snRNA genes in 26,911 individuals with rare disorders.
This revealed de novo (dominant) or biallelic (recessive) RNU2-2 variants in 126 individuals from 108 families.

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Christel Depienne @christeldepienne.bsky.social · Sep 5

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...

Systematic analysis of snRNA genes reveals frequent RNU2-2 variants in dominant and recessive developmental and epileptic encephalopathies

Variants in spliceosomal small nuclear RNA (snRNA) genes RNU4-2 (ReNU syndrome), RNU5B-1 , and RNU2-2 have recently been linked to dominant neurodevelopmental disorders (NDDs), revealing a major, prev...

www.medrxiv.org

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Reposted by Christel Depienne

European Society of Human Genetics @eshg.bsky.social · Jun 27

Today, the Scientific Programme Committee wrapped a fantastic and exciting programme for #eshg2026 conference! More information will available on our conference website soon. We look forward to welcoming you in Gothenburg!

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Reposted by Christel Depienne

Nicky Whiffin @nickywhiffin.bsky.social · May 25

It's time!!!

An entire session of #eshg2025 on snRNA genes ❤️🤓

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Reposted by Christel Depienne

Nicky Whiffin @nickywhiffin.bsky.social · May 25

Next up: Amandine Santini

International study led by
@christeldepienne.bsky.social
145 ReNU syndrome individuals- T-loop variants associated with higher phenotypic severity and more 5'splice site disruption (19 cases).

35 cases/45 controls - identify a shared episignature.

#eshg2025 1/2

www.nature.com

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Reposted by Christel Depienne

Nicky Whiffin @nickywhiffin.bsky.social · Apr 30

Driven by the absolutely incredible families - it is truly amazing and humbling to watch!!

Meet some of them here: www.renusyndrome.org/renu-hope-vi...

❤️🥹

@anneotation.bsky.social @dgmacarthur.bsky.social @christeldepienne.bsky.social #renuCrew

www.renusyndrome.org

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Reposted by Christel Depienne

Nicky Whiffin @nickywhiffin.bsky.social · Apr 11

🚨I could not be more excited to share our new preprint on saturation genome editing of the small nuclear RNA (snRNA) RNU4-2:
www.medrxiv.org/content/10.1...

A super fun collaboration with incredible duo @gregfindlay.bsky.social @joachimdejonghe.bsky.social from @crick.ac.uk
🧬🖥️🩺

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Saturation genome editing of RNU4-2 reveals distinct dominant and recessive neurodevelopmental disorders

Recently, de novo variants in an 18 nucleotide region in the centre of RNU4-2 were shown to cause ReNU syndrome, a syndromic neurodevelopmental disorder (NDD) that is predicted to affect tens of thous...

www.medrxiv.org

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Christel Depienne @christeldepienne.bsky.social · Apr 9

We report a new configuration of repeat expansion in MARCHF6 (FAME3) consisting in elongated TTTTA repeats and only 5-11 TTTCA. This expansion segregates in two unrelated families with myoclonus without epilepsy.

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Christel Depienne @christeldepienne.bsky.social · Apr 9

Happy to share our latest research article published open access in movement disorders movementdisorders.onlinelibrary.wiley.com/doi/epdf/10....

Repeat Expansions with Small TTTCA Insertions in MARCHF6 Cause Familial Myoclonus without Epilepsy

movementdisorders.onlinelibrary.wiley.com

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Reposted by Christel Depienne

European Society of Human Genetics @eshg.bsky.social · Jan 23

One more week until the abstract submission deadline for #eshg2025 #hybridconference! Do not forget to submit your abstract until Thursday, January 30, 2025, 23.59 h CET. All information can be found on our website:
2025.eshg.org/abstracts/
#genetics #genomes

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Reposted by Christel Depienne

Rikke S. Møller @rikkesmoller.bsky.social · Nov 21

I've updated the starter pack for rare genetic epilepsies 🧠🧬

It is a work in progress and I will continue to update the pack over the coming weeks 🤩

go.bsky.app/NXw4e8C

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Reposted by Christel Depienne

ruhrsynapse.bsky.social @ruhrsynapse.bsky.social · Dec 25

For all the Human Genetics folks: ReNU Syndrome has an OMIM page #RNU4-2 @nickywhiffin.bsky.social @christeldepienne.bsky.social
www.omim.org/entry/620851

Online Mendelian Inheritance in Man (OMIM)

Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative compendium of human genes and genetic phenotypes that is freely available and updated daily. The full-text,...

www.omim.org

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Reposted by Christel Depienne

Fyodor Urnov @urnov.bsky.social · Nov 29

Fellow Genetics professors - rejoice! This is pedagogy heaven: the paradigmatic epiallele in calico cats … is built on a cis-regulatory deletion, not a coding mutation!
We can teach it all off 1 paper!
1. Woo
2. Hoooo!!!
H/t @lianafaye.bsky.social

www.biorxiv.org/content/10.1...

Molecular and genetic characterization of sex-linked orange coat color in the domestic cat

The Sex-linked orange mutation in domestic cats causes variegated patches of reddish/yellow hair and is a defining signature of random X-inactivation in female tortoiseshell and calico cats. Unlike th...

www.biorxiv.org

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Reposted by Christel Depienne

Seth Abramson @sethabramson.bsky.social · Nov 17

I learned some stuff about Bluesky I did not know by reading this.

Maybe worth passing it on to others so we can all start getting the full benefit of the 🦋.

Here’s some cool stuff you can do with Bluesky

It’s not just an Alf pics repository.

www.theverge.com

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Reposted by Christel Depienne

Dr Elodie Chabrol @eloscicomm.bsky.social · Nov 15

Vous aimez les podcasts, les scientifiques et la communication scientifique ?

Voici ma petite contribution :
🇫🇷🥼Sous la blouse
🇫🇷🎙Scimple
🇬🇧 🥼Under the lab coat

À écouter :
Sur les plateformes audios
Direct sur mon site
www.elodiechabrol.com/my-podcasts
Ou sur Youtube
youtube.com/@souslablous...

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Reposted by Christel Depienne

Nicky Whiffin @nickywhiffin.bsky.social · Nov 15

I couldn't spot a starter pack for rare disease / clinical genomics, so I started one: go.bsky.app/SUWZ9Hw

Very much a work in progress, and biased by who I have already found here, so please suggest people to add! Self-nominations encouraged.

#ClinicalInformatics #genomics #bioinformatics 🖥️🧬

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