A consortium of thirty-two researchers worldwide, led by Dr Jordi Surrallés, professor of the Department of Genetics and Microbiology at Universitat Autònoma de Barcelona (UAB) and member of the Centre for Biomedical Network Research on Rare Diseases (CIBERER), genetically and clinically characterised almost all Spanish patients suffering from Franconi anaemia, a rare disease affecting one in every 500,000 persons and which is characterised by severe anaemia in children, congenital malformations and a high predisposition to cancer.
A hundred people in Spain suffer from Fanconi anaemia; 80% of these present mutations in the FANCA gene. In the research, 90% of these patients were studied, as well as patients in Brazil, Mexico, Argentina, Peru, United States, United Kingdom, Portugal, Germany, Pakistan and Nigeria.
The research includes characterisation of over 130 pathogenic mutations in the FANCA gene, present in two of every three cases in almost all of the countries analysed, as well as the study of the origin and world distribution of some of the most frequent mutations. The mutation predominating in Spain and in the rest of countries is an ancestral mutation of Indo-European origin which spread throughout Europe thousands of years ago and which reached America across the Atlantic, producing founder effects in areas such as La Palma, with a high prevalence of the disease, and Brazil, where half of all patients share the same gene mutation.
Finally, researchers analysed the effects of the genetic mutations and their clinical impacts. Results indicate that these mutations provoke the absence or dysfunction of FANCA protein, which prevent it from reaching the cell nucleus and activating a DNA repair pathway necessary for genomic stability. This in turn brings about cell death - producing anaemia and abnormal tissue functions - or causes them to develop into tumours. For this reason the study of genes involved in Fanconi anaemia is essential to understand the factors which protect the general population from cancer.
Researchers verified that the fact that mutation produces protein absence or dysfunction does not determine the clinical evolution of anaemia or the severity of the malformative syndrome.
Dr Jordi Surrallés highlights the importance of the study carried out given that results will have significant applications in the diagnosis, prognosis and evolution of this rare disease. For example, several of the mutations described in the article served to carry out prenatal and even pre-implant diagnoses follow by the selection of healthy and compatible embryos, with the aim of using blood from the umbilical cord for bone marrow transplants to cure siblings.