title: Ribosomal protein SA haploinsufficiency in humans with isolated congenital asplenia.
abstract: Isolated congenital asplenia (ICA) is characterized by the absence of a spleen at birth in individuals with no other developmental defects. The patients are prone to life-threatening bacterial infections. The unbiased analysis of exomes revealed heterozygous mutations in RPSA in 18 patients from eight kindreds, corresponding to more than half the patients and over one-third of the kindreds studied. The clinical penetrance in these kindreds is complete. Expression studies indicated that the mutations carried by the patients-a nonsense mutation, a frameshift duplication, and five different missense mutations-cause autosomal dominant ICA by haploinsufficiency. RPSA encodes ribosomal protein SA, a component of the small subunit of the ribosome. This discovery establishes an essential role for RPSA in human spleen development.
authors.affiliation: St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University, New York, NY 10065, USA.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bolze
authors.forename: Nizar
authors.initials: N
authors.lastname: Mahlaoui
authors.forename: Minji
authors.initials: M
authors.lastname: Byun
authors.forename: Bridget
authors.initials: B
authors.lastname: Turner
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Trede
authors.forename: Steven R
authors.initials: SR
authors.lastname: Ellis
authors.forename: Avinash
authors.initials: A
authors.lastname: Abhyankar
authors.forename: Yuval
authors.initials: Y
authors.lastname: Itan
authors.forename: Etienne
authors.initials: E
authors.lastname: Patin
authors.forename: Samuel
authors.initials: S
authors.lastname: Brebner
authors.forename: Paul
authors.initials: P
authors.lastname: Sackstein
authors.forename: Anne
authors.initials: A
authors.lastname: Puel
authors.forename: Capucine
authors.initials: C
authors.lastname: Picard
authors.forename: Laurent
authors.initials: L
authors.lastname: Abel
authors.forename: Lluis
authors.initials: L
authors.lastname: Quintana-Murci
authors.forename: Saul N
authors.initials: SN
authors.lastname: Faust
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Williams
authors.forename: Richard
authors.initials: R
authors.lastname: Baretto
authors.forename: Michael
authors.initials: M
authors.lastname: Duddridge
authors.forename: Usha
authors.initials: U
authors.lastname: Kini
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Pollard
authors.forename: Catherine
authors.initials: C
authors.lastname: Gaud
authors.forename: Pierre
authors.initials: P
authors.lastname: Frange
authors.forename: Daniel
authors.initials: D
authors.lastname: Orbach
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Emile
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Stephan
authors.forename: Ricardo
authors.initials: R
authors.lastname: Sorensen
authors.forename: Alessandro
authors.initials: A
authors.lastname: Plebani
authors.forename: Lennart
authors.initials: L
authors.lastname: Hammarstrom
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Conley
authors.forename: Licia
authors.initials: L
authors.lastname: Selleri
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
mesh_terms: D004252:DNA Mutational Analysis; D056426:Genetic Loci; D057895:Haploinsufficiency; D059446:Heterotaxy Syndrome / Q000235:genetics*; D006801:Humans; D009154:Mutation; D010375:Pedigree; D019683:Penetrance; D017474:Receptors, Laminin / Q000235:genetics*; D012269:Ribosomal Proteins / Q000235:genetics*; D013154:Spleen / Q000002:abnormalities* / Q000254:growth & development
chemical_list: C510624:RPSA protein, human; D017474:Receptors, Laminin; D012269:Ribosomal Proteins