Ribosomal protein L5 and L11 mutations are associated with cleft palate and abnormal thumbs in Diamond-Blackfan anemia patients
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Authors
Gazda, Hanna T.Sheen, Mee Rie
Vlachos, Adrianna
Choesmel, Valerie
O'Donohue, Marie-Francoise
Schneider, Hal
Darras, Natasha
Hasman, Catherine
Sieff, Colin A.
Newburger, Peter E.
Ball, Sarah E.
Niewiadomska, Edyta
Matysiak, Michal
Zaucha, Jan M.
Glader, Bertil
Niemeyer, Charlotte
Meerpohl, Joerg J.
Atsidaftos, Eva
Lipton, Jeffrrey M.
Gleizes, Pierre-Emmanuel
Beggs, Alan H.
UMass Chan Affiliations
Department of PediatricsDocument Type
Journal ArticlePublication Date
2008-12-01Keywords
Anemia, Diamond-BlackfanCleft Palate
Humans
*Mutation
Ribosomal Proteins
Ribosome Subunits, Large
Ribosome Subunits, Small
Thumb
Hematology
Oncology
Pediatrics
Metadata
Show full item recordAbstract
Diamond-Blackfan anemia (DBA), a congenital bone-marrow-failure syndrome, is characterized by red blood cell aplasia, macrocytic anemia, clinical heterogeneity, and increased risk of malignancy. Although anemia is the most prominent feature of DBA, the disease is also characterized by growth retardation and congenital anomalies that are present in approximately 30%-50% of patients. The disease has been associated with mutations in four ribosomal protein (RP) genes, RPS19, RPS24, RPS17, and RPL35A, in about 30% of patients. However, the genetic basis of the remaining 70% of cases is still unknown. Here, we report the second known mutation in RPS17 and probable pathogenic mutations in three more RP genes, RPL5, RPL11, and RPS7. In addition, we identified rare variants of unknown significance in three other genes, RPL36, RPS15, and RPS27A. Remarkably, careful review of the clinical data showed that mutations in RPL5 are associated with multiple physical abnormalities, including craniofacial, thumb, and heart anomalies, whereas isolated thumb malformations are predominantly present in patients carrying mutations in RPL11. We also demonstrate that mutations of RPL5, RPL11, or RPS7 in DBA cells is associated with diverse defects in the maturation of ribosomal RNAs in the large or the small ribosomal subunit production pathway, expanding the repertoire of ribosomal RNA processing defects associated with DBA.Source
Am J Hum Genet. 2008 Dec;83(6):769-80. doi 10.1016/j.ajhg.2008.11.004. Link to article on publisher's websiteDOI
10.1016/j.ajhg.2008.11.004Permanent Link to this Item
http://hdl.handle.net/20.500.14038/43310PubMed ID
19061985Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.ajhg.2008.11.004