| Genetic variants in the noncoding region of RPS19 gene in Diamond-Blackfan anemia: potential implications for phenotypic heterogeneity. | |
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MedLine Citation:
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PMID: 20054847 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Mutations in the RPS19 gene have been identified in 25% of individuals affected by Diamond-Blackfan anemia (DBA), a congenital erythroblastopenia characterized by an aregenerative anemia and a variety of malformations. More than 60 mutations in the five coding exons of RPS19 have been described to date. We previously reported a mutation (c.-1 + 26G>T) and an insertion at -631 upstream of ATG (c.-147_-146insGCCA) in the noncoding region. Because DBA phenotype is extremely heterogeneous from silent to severe and because haploinsufficiency seems to play a role in this process, it is likely that genetic variations in the noncoding regions affecting translation of RPS19 can modulate the phenotypic expression of DBA. However, to date, very few studies have addressed this question comprehensively. In this study, we performed detailed sequence analysis of the RPS19 gene in 239 patients with DBA and 110 of their relatives. We found that 6.2% of the patients with DBA carried allelic variations upstream of ATG: 3.3% with c.-1 + 26G>T; 2.5% with c.-147_-146insGCCA; and 0.4% with c.-174G>A. Interestingly, the c.-147_-146insGCCA, which has been found in a black American and French Caribbean control population, was not found in 500 Caucasian control chromosomes we studied. However, it was found in association with the same haplotype distribution of four intronic polymorphisms in our patients with DBA. Although a polymorphism, the frequency of this variant in the patients with DBA and its association with the same haplotype raises the possibility that this polymorphism and the other genetic variations in the noncoding region could play a role in DBA pathogenesis. |
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Authors:
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Aurore Crétien; Alexis Proust; Jean Delaunay; Patricia Rincé; Thierry Leblanc; Rolande Ducrocq; Maud Simansour; Isabelle Marie; Hannah Tamary; Jörg Meerpohl; Charlotte Niemeyer; Hanna Gazda; Colin Sieff; Sarah Ball; Gil Tchernia; Narla Mohandas; Lydie Da Costa |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: American journal of hematology Volume: 85 ISSN: 1096-8652 ISO Abbreviation: Am. J. Hematol. Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-01-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7610369 Medline TA: Am J Hematol Country: United States |
Other Details:
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Languages: eng Pagination: 111-6 Citation Subset: IM |
Affiliation:
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INSERM U790, Villejuif, France. |
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Descriptor/Qualifier:
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| Grant Support | |
ID/Acronym/Agency:
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HL079565/HL/NHLBI NIH HHS |
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