title: Inherited bone marrow failure syndromes: molecular features.
abstract: Recent advances resulting from the identification of the genes responsible for four inherited marrow failure syndromes, Fanconi anemia, dyskeratosis congenita, Diamond-Blackfan anemia, and Shwachman-Diamond syndrome, are reviewed. The interpretation of genetic testing should be guided by an understanding of the limitations of such testing for each disorder. The possibility of an inherited basis for marrow failure must be considered for adults as well as children with aplastic anemia. Shared molecular themes are emerging from functional studies of the genes underlying the different inherited disorders. Genomic instability may result from impaired DNA repair in Fanconi anemia or telomere dysregulation in dyskeratosis congenita. Mutations affecting ribosome assembly or function are associated with Diamond-Blackfan anemia, dyskeratosis congenita, and Shwachman-Diamond syndrome. These findings raise new questions about the molecular mechanisms regulating hematopoiesis and leukemogenesis. Clinical implications arising from these molecular studies are explored.
authors.affiliation: Children's Hospital Boston, Karp Research Laboratories, Boston, MA 02115, USA. akiko.shimamura@childrens.harvard.edu
authors.forename: Akiko
authors.initials: A
authors.lastname: Shimamura
mesh_terms: D029503:Anemia, Diamond-Blackfan / Q000235:genetics; D001855:Bone Marrow Diseases / Q000175:diagnosis / Q000235:genetics*; D019871:Dyskeratosis Congenita / Q000235:genetics; D005192:Family Health; D005199:Fanconi Anemia / Q000235:genetics; D006801:Humans; D013577:Syndrome