PUBLICATION
Variants in UBAP1L lead to autosomal recessive rod-cone and cone-rod dystrophy
- Authors
- Zeitz, C., Navarro, J., Azizzadeh Pormehr, L., Méjécase, C., Neves, L.M., Letellier, C., Condroyer, C., Albadri, S., Amprou, A., Antonio, A., Ben-Yacoub, T., Wohlschlegel, J., Andrieu, C., Serafini, M., Bianco, L., Antropoli, A., Nassisi, M., El Shamieh, S., Chantot-Bastaraud, S., Mohand-Saïd, S., Smirnov, V., Sahel, J.A., Del Bene, F., Audo, I.
- ID
- ZDB-PUB-240131-17
- Date
- 2024
- Source
- Genetics in medicine : official journal of the American College of Medical Genetics 26(6): 101081 (Journal)
- Registered Authors
- Albadri, Shahad, Del Bene, Filippo
- Keywords
- 3D-modelling, UBAP1L, autosomal recessive rod-cone and cone-rod dystrophy, genome sequencing, novel gene defect, retinal organoids, retinal pigment epithelium, zebrafish
- MeSH Terms
-
- Adult
- Animals
- Cone-Rod Dystrophies*/genetics
- Cone-Rod Dystrophies*/pathology
- Female
- Genes, Recessive
- Humans
- Male
- Mutation/genetics
- Pedigree*
- Phenotype
- Retina/metabolism
- Retina/pathology
- Retinal Cone Photoreceptor Cells/metabolism
- Retinal Cone Photoreceptor Cells/pathology
- Retinal Pigment Epithelium/metabolism
- Retinal Pigment Epithelium/pathology
- Retinal Rod Photoreceptor Cells/metabolism
- Retinal Rod Photoreceptor Cells/pathology
- Retinitis Pigmentosa/genetics
- Retinitis Pigmentosa/pathology
- Tunisia
- Zebrafish*/genetics
- PubMed
- 38293907 Full text @ Genet. Med.
Citation
Zeitz, C., Navarro, J., Azizzadeh Pormehr, L., Méjécase, C., Neves, L.M., Letellier, C., Condroyer, C., Albadri, S., Amprou, A., Antonio, A., Ben-Yacoub, T., Wohlschlegel, J., Andrieu, C., Serafini, M., Bianco, L., Antropoli, A., Nassisi, M., El Shamieh, S., Chantot-Bastaraud, S., Mohand-Saïd, S., Smirnov, V., Sahel, J.A., Del Bene, F., Audo, I. (2024) Variants in UBAP1L lead to autosomal recessive rod-cone and cone-rod dystrophy. Genetics in medicine : official journal of the American College of Medical Genetics. 26(6):101081.
Abstract
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 decent 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 (RPE) 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 four independent autosomal recessive IRD cases from Tunisia. UBAP1L is expressed in the RPE 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 (SOUBA) domain, predicted to interact with ubiquitin. In silico and in vitro studies, including 3D-modeling and ROs revealed that the SOUBA 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping