GPATCH11 variants cause mis-splicing and early-onset retinal dystrophy with neurological impairment

Andrea Zanetti, Gwendal Dujardin, Lucas Fares-Taie, Jeanne Amiel, Jérôme E. Roger, Isabelle Audo, Matthieu P. Robert, Pierre David, Vincent Jung, Nicolas Goudin, Ida Chiara Guerrera, Stéphanie Moriceau, Danielle Amana, Nurit Assia Batzir, Anat Bachar-Zipori, Lina Basel Salmon, Nathalie Boddaert, Sylvain Briault, Ange-Line Bruel, Christine Costet-Fighiera, Luisa Coutinho Santos, Cyril Gitiaux, Karolina Kaminska, Paul Kuentz, Naama Orenstein, Nicole Philip-Sarles, Morgane Plutino, Mathieu Quinodoz, Cristina Santos, Sabine Sigaudy, Mariana Soeiro e Sá, Efrat Sofrin, Ana Berta Sousa, Rui Sousa-Luis, Christel Thauvin-Robinet, Erwin L. van Dijk, Khaoula Zaafrane-Khachnaoui, Dinah Zur, Josseline Kaplan, Carlo Rivolta, Jean-Michel Rozet and Isabelle Perrault ()
Additional contact information
Andrea Zanetti: Imagine and Paris Cité University
Gwendal Dujardin: EFS
Lucas Fares-Taie: Imagine and Paris Cité University
Jeanne Amiel: Imagine and Paris Cité University
Jérôme E. Roger: Paris-Saclay University
Isabelle Audo: National Rare Disease Center REFERET F-
Matthieu P. Robert: APHP
Pierre David: Imagine
Vincent Jung: INSERM US24/CNRS UAR 3633
Nicolas Goudin: INSERM US24/CNRS UAR 3633
Ida Chiara Guerrera: INSERM US24/CNRS UAR 3633
Stéphanie Moriceau: INSERM US24/CNRS UAR 3633, Institute of Genetic Diseases, Imagine
Danielle Amana: Hospital Center of Orleans
Nurit Assia Batzir: Schneider Children’s Medical Center of Israel
Anat Bachar-Zipori: Tel Aviv University
Lina Basel Salmon: Tel Aviv University
Nathalie Boddaert: INSERM UMR1163
Sylvain Briault: Regional Hospital of Orleans (CHRO)
Ange-Line Bruel: CHU Dijon
Christine Costet-Fighiera: Centre d’Ophtalmologie M’Eye Clinic
Luisa Coutinho Santos: Instituto de Oftalmologia Dr. Gama Pinto (IOGP)
Cyril Gitiaux: Paris Cité University
Karolina Kaminska: Institute of Molecular and Clinical Ophthalmology Basel (IOB)
Paul Kuentz: CHU Dijon
Naama Orenstein: Schneider Children’s Medical Center of Israel
Nicole Philip-Sarles: Hospital Timone Enfant
Morgane Plutino: CHU de Nice
Mathieu Quinodoz: Institute of Molecular and Clinical Ophthalmology Basel (IOB)
Cristina Santos: Instituto de Oftalmologia Dr. Gama Pinto (IOGP)
Sabine Sigaudy: Hospital Timone Enfant
Mariana Soeiro e Sá: Centro Hospitalar Universitário Lisboa Norte
Efrat Sofrin: Schneider Children’s Medical Center of Israel
Ana Berta Sousa: Centro Hospitalar Universitário Lisboa Norte
Rui Sousa-Luis: University of Oxford
Christel Thauvin-Robinet: CHU Dijon
Erwin L. van Dijk: Institute for Integrative Biology of the Cell (I2BC)
Khaoula Zaafrane-Khachnaoui: CHU de Nice
Dinah Zur: Tel Aviv University
Josseline Kaplan: Imagine and Paris Cité University
Carlo Rivolta: Institute of Molecular and Clinical Ophthalmology Basel (IOB)
Jean-Michel Rozet: Imagine and Paris Cité University
Isabelle Perrault: Imagine and Paris Cité University

Nature Communications, 2024, vol. 15, issue 1, 1-20

Abstract: Abstract Here we conduct a study involving 12 individuals with retinal dystrophy, neurological impairment, and skeletal abnormalities, with special focus on GPATCH11, a lesser-known G-patch domain-containing protein, regulator of RNA metabolism. To elucidate its role, we study fibroblasts from unaffected individuals and patients carrying the recurring c.328+1 G > T mutation, which specifically removes the main part of the G-patch domain while preserving the other domains. Additionally, we generate a mouse model replicating the patients’ phenotypic defects, including retinal dystrophy and behavioral abnormalities. Our results reveal a subcellular localization of GPATCH11 characterized by a diffuse presence in the nucleoplasm, as well as centrosomal localization, suggesting potential functions in RNA and cilia metabolism. Transcriptomic analysis performed on mouse retina detect dysregulation in both gene expression and splicing activity, impacting key processes such as photoreceptor light responses, RNA regulation, and primary cilia-associated metabolism. Proteomic analysis of mouse retina confirms the roles GPATCH11 plays in RNA processing, splicing, and transcription regulation, while also suggesting additional functions in synaptic plasticity and nuclear stress response. Our research provides insights into the diverse roles of GPATCH11 and identifies that the mutations affecting this protein are responsible for a recently characterized described syndrome.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-54549-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54549-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-54549-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().