Comprehensive analysis of the ABCA4 gene: characterisation of new pathogenic variants

Comprehensive analysis of the ABCA4 gene: characterisation of new pathogenic variants


Dr Esther Pomares.


Dr Marina Riera (Department of Genetics) and Dr AnnikenBurés, Dr Borja Corcóstegui and Dr Rafael Navarro (Department of Retina and Vitreous)

Project description

The vast majority of patients with Stargardt disease, as well as half of recessive cone and rod dystrophy cases, have ABCA4 gene mutations. This gene is also associated with a considerable number of cases of bull’s eye maculopathy and a small number of families with retinitis pigmentosa. All of this points to the ABCA4 gene as a major cause of retinal dystrophies (RD) and, for this reason, considerable work is being carried out on designing effective therapies to combat it.

As most of these treatments are dependent on the type of mutation and the effects produced, prior study and understanding of the variants associated with these retinal dystrophies is an indispensable requirement when it comes to developing the most appropriate therapies in each case.

The search for and identification of variants in the ABCA4 gene is particularly complex due to its large size (50 exons or DNA coding regions) and its high allelic heterogeneity (more than 800 mutations described to date).  It can also have pathogenic variants in intronic or regulatory, i.e. non-coding, regions. In fact, it is estimated that 15-20% of patients are carriers of at least one mutation in these regions which cannot be analysed in conventional genetic studies because of their high complexity.

Preliminary work and new objectives

Recently, the research group of the IMO’s molecular biology laboratory completed a study based on a complete analysis of the 50 exons of the ABCA4 gene in 65 patients. In 23% of the cases, only one pathogenic allele could be identified, which suggested that the second variant could be located in the intronic regions.

For this reason, the objective of the present project is to identify new variants in the non-coding regions of the gene and to complete a genetic diagnosis of the patients with only one mutation in ABCA4. The results of this project will also provide specific epidemiological data on the prevalence of different types of mutations in this gene, information of great value for establishing the molecular bases of these diseases