2. Academic Validation
  3. Ribosomal protein SA haploinsufficiency in humans with isolated congenital asplenia

Ribosomal protein SA haploinsufficiency in humans with isolated congenital asplenia

  • Science. 2013 May 24;340(6135):976-8. doi: 10.1126/science.1234864.
Alexandre Bolze 1,  Nizar Mahlaoui,  Minji Byun,  Bridget Turner,  Nikolaus Trede,  Steven R Ellis,  Avinash Abhyankar,  Yuval Itan,  Etienne Patin,  Samuel Brebner,  Paul Sackstein,  Anne Puel,  Capucine Picard,  Laurent Abel,  Lluis Quintana-Murci,  Saul N Faust,  Anthony P Williams,  Richard Baretto,  Michael Duddridge,  Usha Kini,  Andrew J Pollard,  Catherine Gaud,  Pierre Frange,  Daniel Orbach,  Jean-Francois Emile,  Jean-Louis Stephan,  Ricardo Sorensen,  Alessandro Plebani,  Lennart Hammarstrom,  Mary Ellen Conley,  Licia Selleri,  Jean-Laurent Casanova
Affiliations

Affiliation

  • 1 St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University, New York, NY 10065, USA.
PMID: 23579497 DOI: 10.1126/science.1234864
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.

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