title: Fanconi anemia: a model disease for studies on human genetics and advanced therapeutics.
abstract: Fanconi anemia (FA) is characterized by bone marrow failure, malformations, and chromosome fragility. We review the recent discovery of FA genes and efforts to develop genetic therapies for FA in the last five years. Because current data exclude FANCM as an FA gene, 15 genes remain bona fide FA genes and three (FANCO, FANCR and FANCS) cause an FA like syndrome. Monoallelic mutations in 6 FA associated genes (FANCD1, FANCJ, FANCM, FANCN, FANCO and FANCS) predispose to breast and ovarian cancer. The products of all these genes are involved in the repair of stalled DNA replication forks by unhooking DNA interstrand cross-links and promoting homologous recombination. The genetic characterization of patients with FA is essential for developing therapies, including hematopoietic stem cell transplantation from a savior sibling donor after embryo selection, gene therapy, or genome editing using genetic recombination or engineered nucleases. Newly acquired knowledge about FA promises to provide therapeutic strategies in the near future.
authors.affiliation: Centre for Biomedical Network Research on Rare Diseases (CIBERER), Spain.
authors.forename: Massimo
authors.initials: M
authors.lastname: Bogliolo
authors.affiliation: Genome Instability and DNA Repair Group, Department of Genetics and Microbiology, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Spain. Electronic address: jordi.surralles@uab.cat.
authors.forename: Jordi
authors.initials: J
authors.lastname: Surrallés
mesh_terms: D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D002873:Chromosome Fragility / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics*; D005199:Fanconi Anemia / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D015316:Genetic Therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D009154:Mutation; D017393:RNA Editing / Q000235:genetics
chemical_list: C518295:FANCM protein, human; D004265:DNA Helicases