What is the recently published study by you and your colleagues "The first genetic landscape of inherited retinal dystrophies in Portuguese patients identifies recurrent homozygous mutations as a frequent cause of pathogenesis" about?
In our manuscript, we present the data obtained from a genetic screening of more than 200 patients with inherited retinal dystrophies (IRDs). This study is a result of a joint effort involving clinical and genetic teams from Portugal and Switzerland.
What are inherited retinal dystrophies?
Inherited retinal dystrophies are a group of genetic diseases that affect the light-sensitive tissue in the eye, the retina, leading to lifelong visual impairment. They are known for their elevated genetic and clinical heterogeneity. This means that mutations in one gene can cause a variety of clinical presentations, and there are already more than 280 genes known to be involved in IRDs – a formidable challenge for investigating this class of conditions!
Why is it important to study them?
IRDs are among the most common causes of blindness in Europe. A treatment based on gene therapy has recently been approved for patients carrying mutations in one of these 280 genes. Therefore, knowing exactly which genes and mutations are associated with each patient’s conditions is fundamental in allowing them to be treated or become enrolled in ongoing clinical trials.
What exactly is a genetic landscape and why is it important to describe it for different populations?
A genetic landscape is a large-scale study that provides precise information on the prevalence and assortments of mutations in a given population. For IRDs, the distribution of mutations is often population-specific, and it is not uncommon to uncover DNA changes that are found only in a particular geographical region (we call them “founder mutations”). This is why landscape studies are very useful, both as a basis for future diagnosis of patients, as well as for the broadening of our knowledge on the molecular biology of IRDs globally.
Why did you focus on Portugal in your study?
Surprisingly, the population of Portugal was the only one in Western Europe for which systematic molecular investigation on IRDs had not yet been performed. From our data, we could see that the genetic landscape of Portuguese patients was rather different from those reported in other European populations, including the neighboring Spaniards. It was also interesting to see that, within Portugal, the most frequent mutations (including a possibly founder deletion in the gene EYS, which we discovered in our study) correlated with the geographical origin of patients and their ancestors.
What were your main findings?
I believe that the most important result of our work was the possibility of being able to provide more than 170 patients with a clear molecular diagnosis. Also, the analysis of the distribution and the frequency of these mutations showed that, in many Portuguese patients, their disease was a consequence of a limited number of mutations that originated in specific areas of the country a long time ago.
What did you like most about this research project and how long did it take from start to finish?
The project was initiated in 2017, so, in fact, before I even joined IOB! It’s a great example for collaborative work of scientists and clinicians from different countries, like Dr. Cristina Santos and Prof. Luisa Coutinho Santos from the Instituto de Oftalmologia and Dr. Gama Pinto in Lisbon. And this is what I liked most about it – that it is an international ongoing cooperation with the common goal of helping patients and their families.
Read the entire paper here.