Rare diseases affect less than 1 out of 2.000 people. However, if we take into account the more than 7000 reported rare diseases, the numbers add up to 6% to 8% of global population. In consanguineous populations, the prevalence is much higher, reaching up to 60% (data from FEDER). These pathologies constitute an authentic puzzle: on the one hand, there are only a few patients to study the disease and compare the results of the new treatments. On the other hand, the same pathology may present itself with a variety of clinical traits and genotypes. Even if these illnesses affect all kinds of tissues, one of the organs that accumulates the most rare diseases is, precisely, the eye.

Most of the rare diseases of the eye concern the retina and are gathered under the name of retinal dystrophies (RD). This term comprises a myriad of pathologies with the common trait of vision loss due to a progressive degeneration of the cells in the retina. However, the rest of their characteristics are very different among them. One of said differences is that the damage can be limited to one cellular type or many. The diseases can even take a syndromic nature and harm organs other than the eye, as it is the case of Usher’s syndrome related deafness, or the case of Alport’s syndrome, frequently associated with deafness, hematuria and renal affection. The illnesses may progress at different speeds, from total blindness at a very young age to slower and more gradual vision loss. This clinical diversity goes together with a great genetic heterogeneity. Some diseases, such as Stargardt’s syndrome, are mainly caused by mutations in one unique gene (ABCA4), while Retinitis Pigmentosa, the most frequent RD, can be caused by over sixty different genes and considering the syndromic forms, the number goes up. We should consider not only the mutations located in the exons of the genes, but also the elusive changes hidden in intronic or regulatory regions, which have been gaining importance in the last decades (more information in Berger et al., 2010).

Despite the difficulties that this clinic and genetic heterogenicity imply for their research and treatment, retinal dystrophies have an advantage compared to the rest of rare diseases: the eye is an exceptional research model.  For starters, it is an isolated organ, separated from the rest of the body by a blood-brain barrier that not many drugs are able to cross. However, it is easily accessible, specially when compared to other nervous tissues like the brain or the spinal cord. Even the treatments that require a direct manipulation of the tissue such as intravitreal injections, can be performed without an operating room setting, in a clinic. The same happens with the follow-up of the results, that can be handily checked through eye fundus viewing or measuring the electric response of the cells in the retina (electroretinograms). Lastly, the simple fact of having to eyes each allow for the patient to become their own control, by treating only one eye and comparing the progression of the treatment in both. This way we can limit the problem of the low frequency of the disease in the population, which in turn benefits the development of new therapies.

There are currently over a hundred active clinical trials for the treatment of retinal dystrophies. To participate, specially in the case of gene therapy trials (34), a quality genetic diagnosis is needed, one that identifies with certainty the responsible gene or genes for the disease and the nature of the mutation. The molecular characterization of the pathology secures its clinical diagnosis, establishes its progression, allows genetic counselling and, furthermore, it is an essential step to offer the patient a personalized therapy (gene or cell therapy).

DBGen joins today’s celebration as a drive for the research and treatment of rare diseases. DBGen offers patients and family members a genetic diagnostic of great quality through NGS sequencing, with 16 panels that cover almost 400 genes and complete exome and genome analysis in the case of less common and harder to detect variants.

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