Ribosomal protein SA haploinsufficiency in humans with isolated congenital asplenia

Science. 2013 May 24;340(6135):976-8. doi: 10.1126/science.1234864. Epub 2013 Apr 11.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Mutational Analysis
  • Genetic Loci
  • Haploinsufficiency*
  • Heterotaxy Syndrome / genetics*
  • Humans
  • Mutation
  • Pedigree
  • Penetrance
  • Receptors, Laminin / genetics*
  • Ribosomal Proteins / genetics*
  • Spleen / abnormalities*
  • Spleen / growth & development


  • RPSA protein, human
  • Receptors, Laminin
  • Ribosomal Proteins