Non–Diamond Blackfan Anemia Disorders of Ribosome Function: Shwachman Diamond Syndrome and 5q- Syndrome

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Distinct ribosome maturation defects in yeast models of Diamond-Blackfan anemia and Shwachman-Diamond syndrome.

BACKGROUND Diamond-Blackfan anemia and Shwachman-Diamond syndrome are inherited bone marrow failure syndromes linked to defects in ribosome synthesis. The purpose of this study was to determine whether yeast models for Diamond-Blackfan anemia and Shwachman-Diamond syndrome differed in the mechanism by which ribosome synthesis was affected. DESIGN AND METHODS Northern blotting, pulse-chase ana...

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Defective ribosome assembly in Shwachman-Diamond syndrome.

Shwachman-Diamond syndrome (SDS), a recessive leukemia predisposition disorder characterized by bone marrow failure, exocrine pancreatic insufficiency, skeletal abnormalities and poor growth, is caused by mutations in the highly conserved SBDS gene. Here, we test the hypothesis that defective ribosome biogenesis underlies the pathogenesis of SDS. We create conditional mutants in the essential S...

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Johanson-Blizzard syndrome with Diamond-Blackfan anemia.

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Impaired ribosome biogenesis in Diamond-Blackfan anemia.

The gene encoding the ribosomal protein S19 (RPS19) is frequently mutated in Diamond-Blackfan anemia (DBA), a congenital erythroblastopenia. The consequence of these mutations on the onset of the disease remains obscure. Here, we show that RPS19 plays an essential role in biogenesis of the 40S small ribosomal subunit in human cells. Knockdown of RPS19 expression by siRNAs impairs 18S rRNA synth...

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Neutropenia is a rare complication of Diamond-Blackfan syndrome (congenital hypoplastic anaemia). Three patients are reported: all had neutropenia as well as anaemia, and to investigate the cause of the neutropenia culture of bone marrow for granulocyte-macrophage colony forming cells (GMCFCs) was performed. Two cases had a low incidence of GMCFCs, but the third case had a high incidence. These...

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ژورنال

عنوان ژورنال: Seminars in Hematology

سال: 2011

ISSN: 0037-1963

DOI: 10.1053/j.seminhematol.2011.01.002