Variants in UBAP1L lead to autosomal recessive rod-cone and cone-rod dystrophy.
Genet Med
; 26(6): 101081, 2024 06.
Article
en En
| MEDLINE
| ID: mdl-38293907
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 descent with only few reports of North African descent.METHODS:
Genome, targeted next-generation, and Sanger sequencing was applied to cohort of â¼4000 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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Linaje
/
Pez Cebra
/
Distrofias de Conos y Bastones
Tipo de estudio:
Prognostic_studies
Límite:
Adult
/
Animals
/
Female
/
Humans
/
Male
País/Región como asunto:
Africa
Idioma:
En
Revista:
Genet Med
/
Genet. med
/
Genetics in medicine
Asunto de la revista:
GENETICA MEDICA
Año:
2024
Tipo del documento:
Article