2023-10-30 18:38:11
A simpler, quicker and more effective diagnostic confirmation for Fanconi anemia – a rare genetic disease often associated with serious insufficiency in the production of blood cells, congenital malformations and predisposition to the development of tumors – will be possible thanks to researchers at the Bambino pediatric hospital Jesus of Rome, who identified the ‘epigenetic signature’ of this pathology: a sort of molecular fingerprint referring to the process that influences the ways in which cells read DNA instructions. The improvement of the diagnosis, the IRCCS underlines, represents the starting point for timely management that can guide the family towards specific and effective therapies.
Fanconi anemia is a rare disease that affects one in 200,000 people every year, explains a note. This is the most common genetic condition associated with functional failure of the bone marrow and is often accompanied by congenital malformations and a predisposition to the development of tumors (especially leukemia and epithelial neoplasms). To date, more than twenty genes responsible for the development of this disease have been identified, which varies greatly in symptoms and age of onset, often making the diagnosis particularly complex.
The diagnostic confirmation of Fanconi anemia today occurs through a specific test (Deb test) aimed at highlighting the characteristic chromosomal fragility related to the disease. This test is associated with a genomic analysis, when there is clinical suspicion. This approach may encounter difficulties due to the sensitivity of current methods and the need for specialized skills to interpret the results. Furthermore, the process takes a few weeks before obtaining a result which, in some cases, may not be definitive for the purpose of diagnosis. Now, thanks to an international study coordinated by researchers and clinicians from Bambino Gesù, there is a new tool that allows us to overcome the critical issues linked to the diagnosis of Fanconi anemia. The results were published in the ‘American Journal of Human Genetics’.
Epigenetics – the note recalls – means ‘above genetics’ and therefore indicates something that lies beyond the sequence of genes contained in DNA. Not only that: it studies how the behavior of these genes (their ‘expression’) can be conditioned by external environmental factors, including physical and chemical agents, age, diet, physical activity. Epigenetic modifications are operated by different classes of proteins which directly or indirectly lead to structural changes in DNA, activating or inhibiting the expression of genes. The epigenetic mechanisms that can modify the expression of genes are different and in many cases reversible. For this reason, the study of epigenetics has application implications in clinical practice. Among these, DNA methylation is a molecular switch that regulates the turning on and off of genes, thus influencing the way cells interpret and use genetic information.
The Bambino Gesì researchers studied the DNA methylation profile of the blood cells of subjects with Fanconi anemia. The study, conducted thanks to a collaboration between researchers in Molecular Genetics and Functional Genomics and pediatric clinicians in Oncohematology, Hematopoietic Transplantation and Cellular Therapies, involved a main cohort made up of 25 patients and a second cohort of 14 patients used as a check. The research led to the identification of the specific methylation profile of subjects with Fanconi anemia, i.e. the characteristic epigenetic signature present in their blood cells. The identification of this signature allows us to overcome the limitations of the diagnostic methods used so far. The new tool, also thanks to the development of an algorithm based on artificial intelligence (machine learning), has already been successfully applied to confirm the disease even in those cases in which the diagnosis remained doubtful after the use of classical diagnostic approaches. Furthermore, this approach requires shorter times: about a week.
“We are particularly satisfied with the publication of this study in such a prestigious journal, as it crowns a collaborative project and offers an innovative molecular diagnostic tool for the diagnosis of such a rare disease for which our hospital acts as a reference center national for transplant procedures”, comments Daria Pagliara, first author of the publication and doctor of the Pediatric Oncohematology Area directed by Franco Locatelli. “Thanks to the introduction of genomic technologies – underlines Andrea Ciolfi, co-first author of the work and researcher of the Laboratory of Molecular Genetics and Functional Genomics directed by Marco Tartaglia – today we are able to obtain a diagnosis in more than 60% of patients suffering from diseases orphans of diagnosis, i.e. clinically undefined conditions. Unfortunately, these tests are not infallible due to the current limitations of knowledge or diagnostic tools. This criticality also applies to Fanconi anemia. With the identification of an epigenetic signature in the DNA from the blood cells of patients affected by this disease offers a new tool that allows us to overcome the technical and interpretative limits of the diagnostic approach based on genomic sequencing”.
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