By Lluís Montoliu* (CSIC)
Nobody expects them, almost nobody knows them, but most rare diseases arrive without warning families that, overnight, they come across the name of a pathology that they have generally never heard of before, but that from that moment on will become the center of their lives. And then the questions begin, the fears, the anxieties, the search for culprits, in an attempt to explain the apparently inexplicable.
Why did it touch me and not someone else? Is it my fault or my partner’s? Or both? Are we the only parents who have a child with this rare disease? whatAre there other families like us? Is there anyone researching this rare disease? Is there any treatment? If we had another child, could he also have this same disease?
This is the tough situation faced by many families in which one or more of its members is diagnosed with one of the more than six thousand rare diseases that we know today All extraordinarily diverse, both in the part of the body or organ that they affect and in the severity of the pathology. There are those that are deadly or terribly painful or complex to manage, but there are also those that minimally alter the quality of life. The only thing that all rare diseases share is their low prevalence in the populationan arbitrary value: all those that appear with a frequency of less than one in every two thousand people born.
Lluis Montoliu, author of this post, with a patient with albinism. / Ana Yturralde
question of genes
The the vast majority of rare diseases are genetic in origin. We call them congenital, since they appear from birth. And it is precisely in genetics where you have to look for the cause of them.
We are all mutants. Everybody we carry a multitude of mutations distributed throughout our genome. Now, not all of us manifest or have a disease. We must remember that we have about twenty thousand genes and that, of each gene, we generally have two copies: the one we inherit from our father and the one we inherit from our mother. As long as at least one of the two gene copies works correctly, in principle nothing has to happen. But if the circumstance occurs that a person receives the two copies of the abnormal gene from their parents, the function that that gene should do, the coded protein, will stop being done and then the disease can appear.
There are many exceptions to this described situation, of recessive mutations, which is the most frequent. For example, there are some diseases that already manifest themselves just by inheriting one of the two abnormal copies: are those that we know as dominant inheritance.
When a couple awaits their child with the greatest joy and hope and, shortly after birth, either they or the doctors realize that something is wrong, a journey begins that can take anywhere from a few weeks to years to find the cause of those symptoms. Obtaining a conclusive genetic diagnosis is more complex than it seems, because what we geneticists always do is compare the genome of the person studied with reference genomes. And, of course, depending on which reference genome we use, we can have different results. Besides, It is not true that we only have a few differences between each of us.. The reality is that between one person and another there are between three and six million letter changes. And it is not easy to discover which of these changes is the cause of the disease.
Nor do we know for sure the genetic causes that explain rare diseases. Frequently there are people clinically diagnosed in whom we do not find any mutation. Or, conversely, people who carry mutations that should make them sick, yet are healthy. This suggests to us that We still don’t know everything we need to know about our genome. and the complex interactions that are established between all our genes. And this must be explained to families.
In order to continue advancing in our knowledge about rare diseases and to be able to offer answers to those who suffer from them and their relatives, various investigations are carried out at the CSIC. At the “Alberto Sols” Institute for Biomedical Research, Isabel Varela Nieto studies different types of deafness in mice and Víctor Ruiz studies another rare disease: osteogenesis imperfecta. Paola Bovolenta’s group, from the “Severo Ochoa” Molecular Biology Center, analyzes the genes whose mutations cause rare vision diseases. And I myself, at the National Center for Biotechnology, have spent more than 25 years researching the various types of albinism that we know of. All of these groups are part of the Center for Biomedical Research in the Network for Rare Diseases (CIBERER), of the Carlos III Health Institute.
* Lluís Montoliu eHe is a researcher at the National Center for Biotechnology (CNB) of the CSIC and the Center for Network Biomedical Research in Rare Diseases (CIBERER) of the ISCIII. To try to give an answer to the families that have just heard the news, he has written the book Why does my child have a rare disease? (Next Door Publishers). In it, she collects answers to dozens of questions that she has had the opportunity to answer over the years, talking with many families. He is also the author of other popular titles, such as Color genes, Editing genes: cut, paste and color o albinism.