Incomplete penetrance for isolated congenital asplenia in humans with mutations in translated and untranslated <i>RPSA</i> exons

Abstract

Significance Isolated congenital asplenia (ICA) is characterized by the absence of a spleen at birth without any other developmental defect. ICA predisposes individuals to severe bacterial infections early in childhood. In 2013, we showed that very rare deleterious mutations in the protein-coding region of RPSA, which codes for a protein in the ribosome, caused ICA in 8 of 23 kindreds. We have since enrolled 33 more kindreds and identified 11 new ICA-causing RPSA protein-coding mutations, as well as the first two ICA-causing mutations in the 5′-UTR of this gene. A few individuals carrying one of the new RPSA mutations had a spleen, indicating that mutations in RPSA can cause ICA with incomplete penetrance.