Variants in UBAP1L lead to autosomal recessive rod-cone and cone-rod dystrophy.

Autor:	Zeitz C; Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France. Electronic address: christina.zeitz@inserm.fr., Navarro J; Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France., Azizzadeh Pormehr L; Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France; Mass. Eye and Ear, Ocular Genomics Institute, Berman-Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School, Boston, MA., Méjécase C; Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France; UCL Institute of Ophthalmology, London, UK; The Francis Crick Institute, London, UK., Neves LM; Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France; Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil., Letellier C; Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France., Condroyer C; Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France., Albadri S; Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France., Amprou A; Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France., Antonio A; Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France., Ben-Yacoub T; Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France., Wohlschlegel J; Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France; Department of Biological Structure, University of Washington, Seattle, WA., Andrieu C; Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Centre de Référence Maladies Rares REFERET and INSERM-DGOS CIC 1423, Paris, France., Serafini M; Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France., Bianco L; Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France; Department of Ophthalmology, IRCCS San Raffaele Scientific Institute, Milan, Italy., Antropoli A; Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France; Department of Ophthalmology, IRCCS San Raffaele Scientific Institute, Milan, Italy., Nassisi M; Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France; Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy., El Shamieh S; Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France; Molecular Testing Laboratory, Department of Medical Laboratory Technology, Faculty of Health Sciences, Beirut Arab University, Beirut, Lebanon., Chantot-Bastaraud S; APHP, Hôpital Armand-Trousseau, Département de Génétique, UF de Génétique Chromosomique, Paris, France., Mohand-Saïd S; Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France; Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Centre de Référence Maladies Rares REFERET and INSERM-DGOS CIC 1423, Paris, France., Smirnov V; Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France; Exploration de la Vision et Neuro-Ophtalmologie, CHU de Lille, Lille, France., Sahel JA; Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France; Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Centre de Référence Maladies Rares REFERET and INSERM-DGOS CIC 1423, Paris, France; Department of Ophthalmology, The University of Pittsburgh School of Medicine, Pittsburgh, PA., Del Bene F; Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France., Audo I; Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France; Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Centre de Référence Maladies Rares REFERET and INSERM-DGOS CIC 1423, Paris, France. Electronic address: isabelle.audo@inserm.fr.
Jazyk:	angličtina
Zdroj:	Genetics in medicine : official journal of the American College of Medical Genetics [Genet Med] 2024 Jun; Vol. 26 (6), pp. 101081. Date of Electronic Publication: 2024 Jan 28.
DOI:	10.1016/j.gim.2024.101081
Abstrakt:	Purpose: Progressive inherited retinal degenerations (IRDs) affecting rods and cones are clinically and genetically heterogeneous and can lead to blindness with limited therapeutic options. The major gene defects have been identified in subjects of European and Asian descent with only few reports of North African descent. Methods: Genome, targeted next-generation, and Sanger sequencing was applied to cohort of ∼4000 IRDs cases. Expression analyses were performed including Chip-seq database analyses, on human-derived retinal organoids (ROs), retinal pigment epithelium cells, and zebrafish. Variants' pathogenicity was accessed using 3D-modeling and/or ROs. Results: Here, we identified a novel gene defect with three distinct pathogenic variants in UBAP1L in 4 independent autosomal recessive IRD cases from Tunisia. UBAP1L is expressed in the retinal pigment epithelium and retina, specifically in rods and cones, in line with the phenotype. It encodes Ubiquitin-associated protein 1-like, containing a solenoid of overlapping ubiquitin-associated domain, predicted to interact with ubiquitin. In silico and in vitro studies, including 3D-modeling and ROs revealed that the solenoid of overlapping ubiquitin-associated domain is truncated and thus ubiquitin binding most likely abolished secondary to all variants identified herein. Conclusion: Biallelic UBAP1L variants are a novel cause of IRDs, most likely enriched in the North African population. Competing Interests: Conflict of Interest The authors declare no conflicts of interest. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu