Ribosomal protein SA haploinsufficiency in humans with isolated congenital asplenia
Bolze A., Mahlaoui N., Byun M., Turner B., Trede N., Ellis SR., Abhyankar A., Itan Y., Patin E., Brebner S., Sackstein P., Puel A., Picard C., Abel L., Quintana-Murci L., Faust SN., Williams AP., Baretto R., Duddridge M., Kini U., Pollard AJ., Gaud C., Frange P., Orbach D., Emile JF., Stephan JL., Sorensen R., Plebani A., Hammarstrom L., Conley ME., Selleri L., Casanova JL.
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 encode s ribosomal protein SA, a component of the small subunit of the ribosome. This discovery establishes an essential role for RPSA in human spleen development.