Ribosomal protein SA haploinsufficiency in humans with isolated congenital asplenia.

Journal article

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.

Authors: Bolze, A; Mahlaoui, N; Byun, M; Turner, B; Trede, N

• Publication status: Published
• Journal: Science (New York, N.Y.) More from this journal
• Volume: 340
• Issue: 6135
• Pages: 976-978
• Publication date: 2013-05-01
• DOI: 10.1126/science.1234864
• EISSN: 1095-9203
• ISSN: 0036-8075
• Language: English
• Keywords: Ribosomal Proteins; Mutation; DNA Mutational Analysis; Penetrance; Pedigree; Humans; Heterotaxy Syndrome; Genetic Loci; Spleen; Receptors, Laminin; Haploinsufficiency