Incomplete penetrance for isolated congenital asplenia in humans with mutations in translated and untranslated RPSA exons
Bolze A., Boisson B., Bosch B., Antipenko A., Bouaziz M., Sackstein P., Chaker-Margot M., Barlogis V., Briggs T., Colino E., Elmore AC., Fischer A., Genel F., Hewlett A., Jedidi M., Kelecic J., Krüger R., Ku C-L., Kumararatne D., Lefevre-Utile A., Loughlin S., Mahlaoui N., Markus S., Garcia J-M., Nizon M., Oleastro M., Pac M., Picard C., Pollard AJ., Rodriguez-Gallego C., Thomas C., Von Bernuth H., Worth A., Meyts I., Risolino M., Selleri L., Puel A., Klinge S., Abel L., Casanova J-L.
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.