Identification of new retinal dystrophies genes and characterization of genotype-phenotype correlations

Identification of new retinal dystrophies genes

The aim of this research project is to identify new causative genes of retinal dystrophies, in order to contribute to the knowledge and diagnosis of these diseases.

Research team

Principal: Dr Esther Pomares

Co-researchers: Dra. Paula GaudóDr. Arnau Navinés and Dra. Laura Siles (Genetics Department) and Dr Anniken Burés, Dr Borja Corcóstegui and Dr Rafael Navarro (Retina and Vitreous Department)


Donations from individuals


September 2014 - present

Project description

Retinal dystrophies (RD) are a heterogeneous group of hereditary diseases characterized by the degeneration of photoreceptors and the retinal pigment epithelium. They are one of the main causes of blindness in adults and affect approximately 1 in 3,000 people. These diseases present a high degree of clinical overlap, with very subtle differences between some pathologies; a high genetic heterogeneity, with more than 300 causal genes; and a great phenotypic heterogeneity, since many of these genes are associated with more than one retinal dystrophy.

Despite the high number of genes that can cause RD, they do not explain all cases and, in fact, it is estimated that 20% of the families are carrying mutations in genes that have not yet been identified. This great heterogeneity makes the genetic analysis of RDs extremely complicated, since it is impossible to address them using conventional methodological strategies. For all these reasons, the main objective of this project is the identification of new genes and new mutations responsible for the different types of retinal dystrophies, through the use of recent next generation sequencing technologies, in order to establish new genotype-phenotype correlations and contribute to the knowledge and diagnosis of these diseases.

Current status of the project

June 2022

In the first phase of the project, a genetic analysis tool was designed and developed with high efficiency to identify the molecular causes in different cases of families affected by retinal dystrophies. This new diagnostic methodology, as well as the results obtained, were published in a high impact international scientific journal. Likewise, in later stages, new genotype-phenotype correlations were established for two genes responsible for retinal dystrophies: RP1 and DRAM2.

In both cases, functional and expression studies were performed in order to characterize the identified pathogenic variants, which were also published in international scientific journals of high impact in the field of ophthalmology.

In a second phase of the project, the IMO Foundation research team has identified a new mutation not described to date in the ARSG gene, which was first related in 2018 was related for the first time to Usher Syndrome, a retinal dystrophy that causes visual and hearing loss. These findings have allowed to confirm the existence of a 4th type of the disease, and have been published in the prestigious scientific journal American Journal of Ophthalmology Case Reports.

More recently, our basic research team described the third affected family of SHILCA Syndrome, globally. This syndrome, which occurs with Leber's congenital amaurosis (a type of retinal dystrophy that, despite being a minority disease, causes 20% of school-age blindness) is also related to skeletal and brain anomalies and developmental implications. Our geneticists also described that this syndrome is not always caused by the same genetic alteration, or mutation, but that other variants in the NMNAT1 gene are also related to this disease. All these data were collected in a new scientific article published in the journal International Journal of Molecular Sciences. 

Currently, work continues on the search for new genes and new pathogenic variants responsible for retinal dystrophies and, in addition, the effect caused by each of these variants is being studied and characterized. To do this, different cohorts of patients with mutations in the same gene are being analyzed, and the clinical manifestations of each patient are being compared, in relation to the pathogenic variants they present. This study will allow to establish more precisely the genotype-phenotype correlations of each DR gene. Specifically, some of the cohorts of patients that are currently being studied have mutations in the genes: ABCA4, BEST1, CRB1 or USH2A, among others.

Related research papers

You may be interested in