In recent years a number of human diseases associated with dysregulated ribosome biogenesis have been identified and categorized as âribosomopathiesâ. Acquired or congenital genetic lesions leading to impaired ribosome biogenesis and function appear to be germane to this class of disorders that include Diamond-Blackfan anemia (DBA), a disorder characterized by pure red cell aplasia, Shwachman-Diamond syndrome (SDS), dyskeratosis congenita (DC), cartilage hair hypoplasia (CHH), Treacher Collins syndrome (TCS), and del (5q), a type of myelodysplastic syndrome (MDS). While each of these disorders is associated with distinct mutations in the ribosome biogenesis pathway, bone marrow failure appears to be a uniformly observed clinical symptom. However, the affected lineages appear to be uniquely syndrome-specific. For example, the erythroid and megakaryocytic lineages are affected in DBA and del (5q) MDS, while neutropenia predominates in SDS. From the first identification of disruption of RPS19 (ribosomal protein small subunit 19) in a DBA patient by Dahl et al., limited advances have been made in our understanding of the molecular underpinnings of bone marrow failure syndromes.
Arati Khanna-Gupta, Bone Marrow Failure Syndromes: The Ribosomopathies
Last date updated on July, 2014