Article

First de novo mutation in RPS19 gene as the cause of hydrops fetalis in Diamond-Blackfan anemia

AP-HP, Service d’Hematologie Biologique, H^opital R. Debre,Paris F-75019, France.
American Journal of Hematology (Impact Factor: 3.48). 02/2013; 88(4):340-1. DOI: 10.1002/ajh.23366
Source: PubMed
0 Followers
 · 
63 Views
  • Blood 08/2013; 122(6):856-7. DOI:10.1182/blood-2013-06-508465 · 10.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Diamond Blackfan anemia is a red cell hypoplasia that typically presents within the first year of life. Most cases of Diamond Blackfan anemia are caused by ribosome assembly defects linked to haploinsufficiency for structural proteins of either ribosomal subunit. Nucleolar stress associated with abortive ribosome assembly leads to p53 activation via the interaction of free ribosomal proteins with HDM2, a negative regulator of p53. Significant challenges remain in linking this nucleolar stress signaling pathway to the clinical features of Diamond Blackfan anemia. Defining aspects of disease presentation may relate to developmental and physiological triggers that work in conjunction with nucleolar stress signaling to heighten the p53 response in the developing erythron after birth. The growing number of ribosomopathies provides additional challenges for linking molecular mechanisms with clinical phenotypes. This article is part of a Special Issue entitled: Role of the Nucleolus in Human Disease.
    Biochimica et Biophysica Acta 01/2014; 1842(6). DOI:10.1016/j.bbadis.2013.12.013 · 4.66 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Diamond-Blackfan anemia, Shwachman-Diamond syndrome, and dyskeratosis congenita are inherited syndromes characterized by marrow failure, congenital anomalies, and cancer predisposition. Genetic and molecular studies have uncovered distinct abnormalities in ribosome biogenesis underlying each of these three disorders. How defects in ribosomes, the essential organelles required for protein biosythesis in all cells, cause tissue-specific abnormalities in human disease remains a question of fundamental scientific and medical importance. Here we review the overlapping and distinct clinical features of these three syndromes and discuss current knowledge regarding the ribosomal pathways disrupted in each of these disorders. We also explore the increasing complexity of ribosome biology and how this informs our understanding of developmental biology and human disease.
    Blood 09/2014; 124(18). DOI:10.1182/blood-2014-04-526301 · 10.43 Impact Factor
Show more