Ribosomal Protein S24 Gene Is Mutated in Diamond-Blackfan Anemia

Department of Pediatrics, University of Freiburg, Freiburg, Baden-Württemberg, Germany
The American Journal of Human Genetics (Impact Factor: 10.93). 01/2007; 79(6):1110-8. DOI: 10.1086/510020
Source: PubMed


Diamond-Blackfan anemia (DBA) is a rare congenital red-cell aplasia characterized by anemia, bone-marrow erythroblastopenia, and congenital anomalies and is associated with heterozygous mutations in the ribosomal protein (RP) S19 gene (RPS19) in approximately 25% of probands. We report identification of de novo nonsense and splice-site mutations in another RP, RPS24 (encoded by RPS24 [10q22-q23]) in approximately 2% of RPS19 mutation-negative probands. This finding strongly suggests that DBA is a disorder of ribosome synthesis and that mutations in other RP or associated genes that lead to disrupted ribosomal biogenesis and/or function may also cause DBA.

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Available from: Jeffrey Lipton
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    • "In zebrafish and mice, reduced ribosomal protein function results in defects affecting brain, skeleton, eye, and ear development (Amsterdam et al., 2004; Oliver et al., 2004; Uechi et al., 2006; McGowan et al., 2008; Kondrashov et al., 2011; Watkins-Chow et al., 2013). In humans, Diamond-Blackfan anemia and isolated congenital asplenia are associated with mutations in ribosomal proteins (Draptchinskaia et al., 1999; Willig et al., 1999; Gazda et al., 2006, 2008; Farrar et al., 2008; Bolze et al., 2013). Different models have been proposed to explain ribosomal protein mutant phenotypes, including ribosome heterogeneity, extraribosomal function, and targeting of specific transcripts for translational regulation (Byrne, 2009; Warner and McIntosh, 2009; Horiguchi et al., 2012; Xue and Barna, 2012). "
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