RGD Reference Report - Abnormalities of the large ribosomal subunit protein, Rpl35a, in Diamond-Blackfan anemia. - Rat Genome Database

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Abnormalities of the large ribosomal subunit protein, Rpl35a, in Diamond-Blackfan anemia.

Authors: Farrar, JE  Nater, M  Caywood, E  McDevitt, MA  Kowalski, J  Takemoto, CM  Talbot CC, JR  Meltzer, P  Esposito, D  Beggs, AH  Schneider, HE  Grabowska, A  Ball, SE  Niewiadomska, E  Sieff, CA  Vlachos, A  Atsidaftos, E  Ellis, SR  Lipton, JM  Gazda, HT  Arceci, RJ 
Citation: Farrar JE, etal., Blood. 2008 Sep 1;112(5):1582-92. doi: 10.1182/blood-2008-02-140012. Epub 2008 Jun 5.
RGD ID: 11535069
Pubmed: PMID:18535205   (View Abstract at PubMed)
PMCID: PMC2518874   (View Article at PubMed Central)
DOI: DOI:10.1182/blood-2008-02-140012   (Journal Full-text)

Diamond-Blackfan anemia (DBA) is an inherited bone marrow failure syndrome characterized by anemia, congenital abnormalities, and cancer predisposition. Small ribosomal subunit genes RPS19, RPS24, and RPS17 are mutated in approximately one-third of patients. We used a candidate gene strategy combining high-resolution genomic mapping and gene expression microarray in the analysis of 2 DBA patients with chromosome 3q deletions to identify RPL35A as a potential DBA gene. Sequence analysis of a cohort of DBA probands confirmed involvement RPL35A in DBA. shRNA inhibition shows that Rpl35a is essential for maturation of 28S and 5.8S rRNAs, 60S subunit biogenesis, normal proliferation, and cell survival. Analysis of pre-rRNA processing in primary DBA lymphoblastoid cell lines demonstrated similar alterations of large ribosomal subunit rRNA in both RPL35A-mutated and some RPL35A wild-type patients, suggesting additional large ribosomal subunit gene defects are likely present in some cases of DBA. These data demonstrate that alterations of large ribosomal subunit proteins cause DBA and support the hypothesis that DBA is primarily the result of altered ribosomal function. The results also establish that haploinsufficiency of large ribosomal subunit proteins contributes to bone marrow failure and potentially cancer predisposition.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Diamond-Blackfan anemia 5  IAGP 11535069DNA:deletions and snps:multiple (human)RGD 
Diamond-Blackfan anemia 5  ISORPL35A (Homo sapiens)11535069; 11535069DNA:deletions and snps:multiple (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Anemia  IAGP 11535069DNA:deletions and snps:multiple (human)RGD 
Erythroid hypoplasia  IAGP 11535069DNA:deletions and snps:multiple (human)RGD 
Reticulocytopenia  IAGP 11535069DNA:deletions and snps:multiple (human)RGD 
Objects Annotated

Genes (Rattus norvegicus)
Rpl35a  (ribosomal protein L35A)

Genes (Mus musculus)
Rpl35a  (ribosomal protein L35A)

Genes (Homo sapiens)
RPL35A  (ribosomal protein L35a)


Additional Information