Back to news
Research / 23 April 2024

Identification of the UBAP1L gene as associated with genetic retinal dystrophies

Genetic retinal dystrophies (GRDs) represent a heterogeneous group of genetic pathologies that can lead to blindness with limited therapeutic options. At the Institut de la Vision, Christina Zeitz and Isabelle Audo identified a new genetic defect associated with GRDs in patients from a cohort of over 4000 subjects mainly followed at the Referet Center for Rare Diseases at the Hôpital national des 15-20. This work is the subject of a publication in the journal Genetics in Medicine.



The researchers used various sequencing techniques, including next-generation sequencing and Sanger sequencing, to analyze the genome of these cases of GRDs. The use of two models, one derived from induced pluripotent stem cells from a patient developed into retinal organoids and pigment epithelium cells, the other from zebrafish developed by Filippo Del Bene at the Institut de la Vision, allowed for expression analyses and validation of the role of this new gene in GRDs in the retina.

UBAP1L, UBAP1 and ubiquitin

The essential discovery of this study concerns the identification of mutations in a gene, UBAP1L, causing GRDs in four patients of Tunisian origin. This gene encodes a protein similar to the UBAP1 protein, associated with a small molecule called ubiquitin. Ubiquitin is involved in the elimination of abnormal proteins and is essential for cell function. 

UBAP1L is thought to play an important role in the retina with specific expression in light-sensitive cells, photoreceptors, leading to their degeneration in case of mutations. Researchers studied the impact of mutations on protein function through 3D modeling using bioinformatics programs and using retinal organoid and pigment epithelium cells. The researchers will now continue these studies on the two developed models, pluripotent stem cells and zebrafish, to better elucidate the molecular pathways associated with UBAP1L in the retina.


In conclusion, this research highlights the role of a new gene, UBAP1L, mutations of which represent a potential cause of GRDs. Studying this gene in other cohorts will determine the prevalence of the genetic defect and its geographical distribution. These genetic discoveries contribute to a better understanding of the complex pathologies of genetic retinal dystrophies and, ultimately, to improving their management.