title: The genomics of inherited bone marrow failure: from mechanism to the clinic.
abstract: The inherited bone marrow failure syndromes (IBMFS) typically present with significant cytopenias in at least one haematopoietic cell lineage that may progress to pancytopenia, and are associated with increased risk of cancer. Although the clinical features of the IBMFS are often diagnostic, variable disease penetrance and expressivity may result in diagnostic dilemmas. The discovery of the genetic aetiology of the IBMFS has been greatly facilitated by next-generation sequencing methods. This has advanced understanding of the underlying biology of the IBMFS and been essential in improving clinical management and genetic counselling for affected patients. Herein we review the clinical features, underlying biology, and new genomic discoveries in the IBMFS, including Fanconi anaemia, dyskeratosis congenita, Diamond Blackfan anaemia, Shwachman Diamond syndrome and some disorders of the myeloid and megakaryocytic lineages.
authors.affiliation: Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.|Research Division, Instituto Nacional de Cancerologia, Mexico City, Mexico.
authors.forename: Talia
authors.initials: T
authors.lastname: Wegman-Ostrosky
authors.affiliation: Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Savage
mesh_terms: D000741:Anemia, Aplastic / Q000175:diagnosis / Q000235:genetics*; D029503:Anemia, Diamond-Blackfan / Q000175:diagnosis / Q000235:genetics; D001791:Blood Platelet Disorders / Q000175:diagnosis / Q000235:genetics; D001855:Bone Marrow Diseases / Q000175:diagnosis / Q000235:genetics*; D000080983:Bone Marrow Failure Disorders; D049914:DNA Repair-Deficiency Disorders / Q000235:genetics; D019871:Dyskeratosis Congenita / Q000175:diagnosis / Q000235:genetics; D010188:Exocrine Pancreatic Insufficiency / Q000175:diagnosis / Q000235:genetics; D005199:Fanconi Anemia / Q000175:diagnosis / Q000235:genetics; D005817:Genetic Counseling; D023281:Genomics / Q000379:methods*; D006457:Hemoglobinuria, Paroxysmal / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008068:Lipomatosis / Q000175:diagnosis / Q000235:genetics; D009503:Neutropenia / Q000151:congenital / Q000175:diagnosis / Q000235:genetics; D012270:Ribosomes / Q000235:genetics; D000081003:Shwachman-Diamond Syndrome; D016615:Telomere / Q000235:genetics
keywords: Diamond Blackfan anaemia; Fanconi anaemia; Shwachman Diamond syndrome; dyskeratosis congenita; inherited bone marrow failure