An international team of researchers has made significant progress in the study of Fanconi anaemia, a rare autosomal recessive genetic condition. The researchers managed to describe the function and range of possible mutations of the gene implicated in this rare disease, which affects functions such as nerve and skeletal development, blood cell formation and predisposition to cancer. With this discovery, the team hopes that detecting the defective gene that causes Fanconi anaemia will become easier - this is fundamental in prenatal and pre-implantation diagnosis, where the objective is to select an embryo compatible with a transplant donor. Furthermore, the identification of the responsible gene could prove crucial for the future application of gene therapy. According to the researchers, 'The result is a step forward in the knowledge of the genetics and molecular biology of this disease which, although rare, is of important biomedical interest because the proteins that are implicated with it are also associated with different vital functions and cancer suppression.' The researchers studied the function and mutational spectrum of the FANCD2 gene, one of 13 genes implicated in Fanconi anaemia. Their work covered molecular studies of all the D2 Fanconi patients (those affected by the Fanconi anaemia that present alternations of this gene) known around the world. They also compared FANCD2 patients with 754 patients with FANCA, FANCC and FANCG, which are more prevalent variants found around the world. The results indicated that the Fanconi D2 patients' symptoms (clinical phenotype) were more severe than those of the others. For the researchers, this is due to the vital function that the FANCD2 gene plays in maintaining the stability of the genome, and in the development and function of the multiple organs and tissues (the formation of white blood cells, platelets and other elements of the blood, neuronal development or the formation of skeletal tissue). In addition, the progression of the disease is more rapid in Fanconi D2 patients, resulting in a need for early transfusions, and transplants when there is a compatible donor. The researchers also found that the mutations do not totally eliminate the FANCD2 gene function, but cause a low level of expression of the FANCD2 protein. These results indicate that in humans, as opposed to what was observed in mice, the total absence of the FANCD2 protein is impossible (without this protein the embryo will not develop). The results also show that animal models do not always reflect the clinical phenotype of the disease. The study was led by Dr Jordi Surrallés of the Autonomous University of Barcelona, and included 13 European and North American laboratories and hospitals. It was published in the May edition of the American Journal of Human Genetics.