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
  • 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.