The Inherited Bone Marrow Failure Syndromes: Fanconi Anemia, Dyskeratosis Congenita and Diamond‐Blackfan Anemia

Abstract

The inherited bone marrow (BM) failure syndromes, Fanconi anemia (FA), dyskeratosis congenita (DC) and Diamond–Blackfan anemia (DBA), are genetic disorders in which patients develop BM failure at a high frequency, usually in association with a number of somatic abnormalities. The recent identification of four FA genes (FANCA, FANCC, FANCF, FANCG), one DC gene (DKC1) and one DBA gene (RPS19) has confirmed their genetic heterogeneity and has provided new methods of diagnosis; this is particularly useful where clinical presentation is atypical, as in the Hoyeraal–Hreidarsson syndrome, a severe variant of X-linked DC. Recent data suggest that the FA proteins function in a novel cell pathway which has an important role in maintaining genomic stability; the DKC1 encoded nucleolar protein, dyskerin, is predicted to have an important role in ribosomal RNA (rRNA) processing and the RPS19 protein is a structural ribosomal protein. These syndromes therefore provide important information about novel cell pathways which may lead to a better understanding of normal hematopoiesis and of the poorly understood idiopathic aplastic anemia (AA). In turn, this may lead to new treatments, not only for FA, DC and DBA, but also for some types of idiopathic AA.