Genomic DNA from 57 DBA patients and their first-degree relatives was sequenced for mutations in RPS19, RPS10, RPS24, RPS26, RPS7, RPS17, RPL5, RPL11, RPL35a, and GATA1.
The present analyses demonstrate that the comprehensive regulatory network we constructed is useful for the functional prediction of new and important miRNAs in DBA and will provide insights into the pathogenesis of mutant rps24-mediated human DBA disease.
In addition, we detected five deletions in RP genes in which mutations have been previously shown to cause DBA: one each in RPS19, RPS24, and RPS26, and two in RPS17.
In addition, we detected five deletions in RP genes in which mutations have been previously shown to cause DBA: one each in RPS19, RPS24, and RPS26, and two in RPS17.
Recent advances in identifying the genetic abnormalities underlying DBA have demonstrated involvement of genes encoding both large (RPL) and small (RPS) ribosomal subunit proteins, including mutations of RPL5, RPL11, RPL35A, RPS7, RPS10, RPS17, RPS19, RPS24, and RPS26 in 50% to 60% of affected patients.
In this genotype-phenotype analysis we screened the coding sequence and intron-exon boundaries of RPS14, RPS16, RPS24, RPL5, RPL11, and RPL35A in 92 Italian patients with Diamond-Blackfan anemia who were negative for RPS19 mutations.
We screened 49 Japanese patients with Diamond-Blackfan anemia (45 probands) for mutations in the six known genes associated with Diamond-Blackfan anemia: RPS19, RPS24, RPS17, RPL5, RPL11, and RPL35A.
We show herein that primary fibroblasts from DBA patients with truncating mutations in RPS19 or in RPS24 have a marked reduction in proliferative capacity.
We show herein that primary fibroblasts from DBA patients with truncating mutations in RPS19 or in RPS24 have a marked reduction in proliferative capacity.
Mutations in ribosomal proteins RPS19, RPS24 and RPS17 have been reported in Diamond-Blackfan Anemia (DBA), an autosomal dominant disease characterised by pure red cell aplasia.
Three genes encoding ribosomal proteins have been associated to DBA: after RPS19, mutations in genes RPS24 and RPS17 were recently identified in a fraction of the patients.
Three genes encoding ribosomal proteins have been associated to DBA: after RPS19, mutations in genes RPS24 and RPS17 were recently identified in a fraction of the patients.
Currently two genes are associated with the DBA phenotype--the ribosomal protein (RP) S19 mutated in 25% of DBA patients and RPS24 mutated in approximately 1.4% of DBA patients.