title: Ribosomal protein genes RPS10 and RPS26 are commonly mutated in Diamond-Blackfan anemia.
abstract: 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.
authors.affiliation: Division of Genetics and Program in Genomics, The Manton Center for Orphan Disease Research, Children's Hospital Boston, Boston, MA 02115, USA.
authors.forename: Leana
authors.initials: L
authors.lastname: Doherty
authors.forename: Mee Rie
authors.initials: MR
authors.lastname: Sheen
authors.forename: Adrianna
authors.initials: A
authors.lastname: Vlachos
authors.forename: Valerie
authors.initials: V
authors.lastname: Choesmel
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: O'Donohue
authors.forename: Catherine
authors.initials: C
authors.lastname: Clinton
authors.forename: Hal E
authors.initials: HE
authors.lastname: Schneider
authors.forename: Colin A
authors.initials: CA
authors.lastname: Sieff
authors.forename: Peter E
authors.initials: PE
authors.lastname: Newburger
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Ball
authors.forename: Edyta
authors.initials: E
authors.lastname: Niewiadomska
authors.forename: Michal
authors.initials: M
authors.lastname: Matysiak
authors.forename: Bertil
authors.initials: B
authors.lastname: Glader
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Arceci
authors.forename: Jason E
authors.initials: JE
authors.lastname: Farrar
authors.forename: Eva
authors.initials: E
authors.lastname: Atsidaftos
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Lipton
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Gleizes
authors.forename: Hanna T
authors.initials: HT
authors.lastname: Gazda
mesh_terms: D029503:Anemia, Diamond-Blackfan / Q000235:genetics*; D001483:Base Sequence; D006801:Humans; D009154:Mutation / Q000235:genetics*; D012323:RNA Processing, Post-Transcriptional; D012269:Ribosomal Proteins / Q000235:genetics*
chemical_list: C489203:RPS26 protein, human; D012269:Ribosomal Proteins