Ribosomal protein genes RPS10 and RPS26 are commonly mutated in Diamond-Blackfan anemia
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Authors
Doherty, LeanaSheen, Mee Rie
Vlachos, Adrianna
Choesmel, Valerie
O'Donohue, Marie-Francoise
Clinton, Catherine
Schneider, Hal E.
Sieff, Colin A.
Newburger, Peter E.
Ball, Sarah E.
Niewiadomska, Edyta
Matysiak, Michal
Glader, Bertil
Arceci, Robert J.
Farrar, Jason E.
Atsidaftos, Eva
Lipton, Jeffrrey M.
Gleizes, Pierre-Emmanuel
Gazda, Hanna T.
UMass Chan Affiliations
Department of PediatricsDocument Type
Journal ArticlePublication Date
2010-02-12Keywords
Anemia, Diamond-BlackfanBase Sequence
Humans
Mutation
RNA Processing, Post-Transcriptional
Ribosomal Proteins
Hematology
Oncology
Pediatrics
Metadata
Show full item recordAbstract
Diamond-Blackfan anemia (DBA), an inherited bone marrow failure syndrome characterized by anemia that usually presents before the first birthday or in early childhood, is associated with birth defects and an increased risk of cancer. Although anemia is the most prominent feature of DBA, the disease is also characterized by growth retardation and congenital malformations, in particular craniofacial, upper limb, heart, and urinary system defects that are present in approximately 30%-50% of patients. DBA has been associated with mutations in seven ribosomal protein (RP) genes, RPS19, RPS24, RPS17, RPL35A, RPL5, RPL11, and RPS7, in about 43% of patients. To continue our large-scale screen of RP genes in a DBA population, we sequenced 35 ribosomal protein genes, RPL15, RPL24, RPL29, RPL32, RPL34, RPL9, RPL37, RPS14, RPS23, RPL10A, RPS10, RPS12, RPS18, RPL30, RPS20, RPL12, RPL7A, RPS6, RPL27A, RPLP2, RPS25, RPS3, RPL41, RPL6, RPLP0, RPS26, RPL21, RPL36AL, RPS29, RPL4, RPLP1, RPL13, RPS15A, RPS2, and RPL38, in our DBA patient cohort of 117 probands. We identified three distinct mutations of RPS10 in five probands and nine distinct mutations of RPS26 in 12 probands. Pre-rRNA analysis in lymphoblastoid cells from patients bearing mutations in RPS10 and RPS26 showed elevated levels of 18S-E pre-rRNA. This accumulation is consistent with the phenotype observed in HeLa cells after knockdown of RPS10 or RPS26 expression with siRNAs, which indicates that mutations in the RPS10 and RPS26 genes in DBA patients affect the function of the proteins in rRNA processing. Elsevier Inc. All rights reserved.Source
Am J Hum Genet. 2010 Feb 12;86(2):222-8. Epub 2010 Jan 28. Link to article on publisher's websiteDOI
10.1016/j.ajhg.2009.12.015Permanent Link to this Item
http://hdl.handle.net/20.500.14038/43326PubMed ID
20116044Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.ajhg.2009.12.015