Christel Depienne
@christeldepienne.bsky.social
Molecular geneticist | Neurogenetics | repeat expansions | chromosome X | snRNAs | and more
It represents the PhD work of Pierre Tilliole (Godin lab) and Carolin Mattausch (my group) with the contribution from Elsa Leitão .
Many thanks to all 3 of them, to Juliette, to all families who participated, clinicians and all collaborators who made this long-term effort possible. 🙏
Many thanks to all 3 of them, to Juliette, to all families who participated, clinicians and all collaborators who made this long-term effort possible. 🙏
October 26, 2025 at 3:53 AM
It represents the PhD work of Pierre Tilliole (Godin lab) and Carolin Mattausch (my group) with the contribution from Elsa Leitão .
Many thanks to all 3 of them, to Juliette, to all families who participated, clinicians and all collaborators who made this long-term effort possible. 🙏
Many thanks to all 3 of them, to Juliette, to all families who participated, clinicians and all collaborators who made this long-term effort possible. 🙏
These results highlight functional retrocopies as an overlooked layer of genetic robustness and evolutionary innovation in mammalian brain development.
This study is the result of >10 years of work in my group, in close collaboration with Juliette Godin’s group at IGBMC, Strasbourg.
This study is the result of >10 years of work in my group, in close collaboration with Juliette Godin’s group at IGBMC, Strasbourg.
October 26, 2025 at 3:53 AM
These results highlight functional retrocopies as an overlooked layer of genetic robustness and evolutionary innovation in mammalian brain development.
This study is the result of >10 years of work in my group, in close collaboration with Juliette Godin’s group at IGBMC, Strasbourg.
This study is the result of >10 years of work in my group, in close collaboration with Juliette Godin’s group at IGBMC, Strasbourg.
🧠Pathogenic RBMX variants perturb cortical development through both partial loss-of-function and gain-of-function mechanisms.
October 26, 2025 at 3:53 AM
🧠Pathogenic RBMX variants perturb cortical development through both partial loss-of-function and gain-of-function mechanisms.
🐁Mice possess two Rbmxl1 retrocopies that arose independently from the human RBMXL1. Rbmx-deficient mice exhibit unexpectedly mild cortical phenotypes mirroring the defects seen in patients, likely due to better compensation by Rbmxl1.
October 26, 2025 at 3:53 AM
🐁Mice possess two Rbmxl1 retrocopies that arose independently from the human RBMXL1. Rbmx-deficient mice exhibit unexpectedly mild cortical phenotypes mirroring the defects seen in patients, likely due to better compensation by Rbmxl1.
👯♂️RBMX and RBMXL1 are both expressed during brain development, share protein and RNA partners and function, and act redundantly during corticogenesis.
October 26, 2025 at 3:53 AM
👯♂️RBMX and RBMXL1 are both expressed during brain development, share protein and RNA partners and function, and act redundantly during corticogenesis.
🧬RBMX has a close autosomal retrocopy, RBMXL1, sharing ~95% sequence identity with RBMX in humans
October 26, 2025 at 3:53 AM
🧬RBMX has a close autosomal retrocopy, RBMXL1, sharing ~95% sequence identity with RBMX in humans
🧬Hemizygous RBMX variants on chromosome X cause neurodevelopmental disorders in males, with intellectual disability, microcephaly, brain malformations, and microphthalmia.
October 26, 2025 at 3:53 AM
🧬Hemizygous RBMX variants on chromosome X cause neurodevelopmental disorders in males, with intellectual disability, microcephaly, brain malformations, and microphthalmia.
Using human genetics and complementary ex vivo, in vitro, and in vivo functional approaches, we uncover a critical role for the RBMX retrocopy, RBMXL1, in brain development, possibly also modulating the phenotype associated with pathogenic RBMX variants.
October 26, 2025 at 3:53 AM
Using human genetics and complementary ex vivo, in vitro, and in vivo functional approaches, we uncover a critical role for the RBMX retrocopy, RBMXL1, in brain development, possibly also modulating the phenotype associated with pathogenic RBMX variants.
Congrats to you as well!
Amazing to see how different approaches led to outcomes that are both similar and wonderfully complementary 😊
Amazing to see how different approaches led to outcomes that are both similar and wonderfully complementary 😊
September 8, 2025 at 12:59 PM
Congrats to you as well!
Amazing to see how different approaches led to outcomes that are both similar and wonderfully complementary 😊
Amazing to see how different approaches led to outcomes that are both similar and wonderfully complementary 😊
Link to
Our previous article: www.nature.com/articles/s41...
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
September 5, 2025 at 3:52 PM
Link to
Our previous article: www.nature.com/articles/s41...
Our previous article: www.nature.com/articles/s41...
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
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
September 5, 2025 at 3:50 PM
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
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
This study brought together >200 collaborators worldwide and would not have been possible without the contribution of the Plan France Médecine Génomique (PFMG). 🙏
September 5, 2025 at 3:47 PM
This study brought together >200 collaborators worldwide and would not have been possible without the contribution of the Plan France Médecine Génomique (PFMG). 🙏
Importantly, these findings are independently supported by two other preprints, including one posted the exact same day:
📄 www.medrxiv.org/content/10.1...
📄 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
September 5, 2025 at 3:46 PM
Importantly, these findings are independently supported by two other preprints, including one posted the exact same day:
📄 www.medrxiv.org/content/10.1...
📄 www.medrxiv.org/content/10.1...
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),
Our results support a continuum between dominant and recessive disorders and establish RNU2-2 DEE as nearly as frequent as ReNU syndrome (RNU4-2),
September 5, 2025 at 3:46 PM
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),
Our results support a continuum between dominant and recessive disorders and establish RNU2-2 DEE as nearly as frequent as ReNU syndrome (RNU4-2),
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.
It often arises from a de novo variant in trans with an inherited allele, reflecting the high mutability of snRNA genes.
September 5, 2025 at 3:44 PM
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.
It often arises from a de novo variant in trans with an inherited allele, reflecting the high mutability of snRNA genes.
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.
This revealed de novo (dominant) or biallelic (recessive) RNU2-2 variants in 126 individuals from 108 families.
September 5, 2025 at 3:43 PM
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.
This revealed de novo (dominant) or biallelic (recessive) RNU2-2 variants in 126 individuals from 108 families.
Reposted by Christel Depienne
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
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
May 25, 2025 at 9:29 AM
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
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
Reposted by Christel Depienne
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
Meet some of them here: www.renusyndrome.org/renu-hope-vi...
❤️🥹
@anneotation.bsky.social @dgmacarthur.bsky.social @christeldepienne.bsky.social #renuCrew
www.renusyndrome.org
April 30, 2025 at 9:53 AM
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
Meet some of them here: www.renusyndrome.org/renu-hope-vi...
❤️🥹
@anneotation.bsky.social @dgmacarthur.bsky.social @christeldepienne.bsky.social #renuCrew
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.
April 9, 2025 at 7:24 PM
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.