Ribosomal Protein SA Haploinsufficiency in Humans with Isolated Congenital Asplenia

• Published in: Science (American Association for the Advancement of Science) Vol. 340; no. 6135; pp. 976 - 978
• Main Authors: Bolze, Alexandre, Mahlaoui, Nizar, Byun, Minji, Turner, Bridget, Trede, Nikolaus, Ellis, Steven R., Abhyankar, Avinash, Itan, Yuval, Patin, Etienne, Brebner, Samuel, Sackstein, Paul, Puel, Anne, Picard, Capucine, Abel, Laurent, Quintana-Murci, Lluis, Faust, Saul N., Williams, Anthony P., Baretto, Richard, Duddridge, Michael, Kini, Usha, Pollard, Andrew J., Gaud, Catherine, Frange, Pierre, Orbach, Daniel, Emile, Jean-Francois, Stephan, Jean-Louis, Sorensen, Ricardo, Plebani, Alessandro, Hammarstrom, Lennart, Conley, Mary Ellen, Selleri, Licia, Casanova, Jean-Laurent
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 24.05.2013; The American Association for the Advancement of Science
• Subjects: abnormal development; Abnormalities; Alleles; Bacteria; Bacterial diseases; bacterial infections; Congenital diseases; disease incidence; DNA Mutational Analysis; Genes; Genetic Loci; Genetic mutation; Genetics; Haploinsufficiency; Heterotaxy Syndrome - genetics; Human; Humans; Missense mutation; Mutation; Mutations; P values; Patients; Pediatrics; Pedigree; Penetrance; Proteins; Receptors, Laminin - genetics; Ribonucleic acid; Ribosomal proteins; Ribosomal Proteins - genetics; risk; RNA; sequence analysis; Spleen; Spleen - abnormalities; Spleen - growth & development; T lymphocytes
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.1234864

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 exornes 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.