Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/48610
Title: Incomplete penetrance for isolated congenital asplenia in humans with mutations in translated and untranslated RPSA exons
Authors: Bolze, Alexandre
Boisson, Bertrand
Bosch, Barbara
Antipenko, Alexander
Bouaziz, Matthieu
Sackstein, Paul
Chaker-Margot, Malik
Barlogis, Vincent
Briggs, Tracy
Colino, Elena
Elmore, Aurora C.
Fischer, Alain
Genel, Ferah
Hewlett, Angela
Jedidi, Maher
Kelecic, Jadranka
Krüger, Renate
Ku, Cheng Lung
Kumararatne, Dinakantha
Lefevre-Utile, Alain
Loughlin, Sam
Mahlaoui, Nizar
Markus, Susanne
Garcia, Juan Miguel
Nizon, Mathilde
Oleastro, Matias
Pac, Malgorzata
Picard, Capucine
Pollard, Andrew J.
Rodriguez-Gallego, Carlos 
Thomas, Caroline
Bernuth, Horst Von
Worth, Austen
Meyts, Isabelle
Risolino, Maurizio
Selleri, Licia
Puel, Anne
Klinge, Sebastian
Abel, Laurent
Casanova, Jean Laurent
UNESCO Clasification: 32 Ciencias médicas
3205 Medicina interna
Keywords: Isolated congenital asplenia
Spleen
incomplete penetranceI
Ribosomopathy
RPSA
Issue Date: 2018
Journal: Proceedings of the National Academy of Sciences of the United States of America 
Abstract: Isolated congenital asplenia (ICA) is the only known human developmental defect exclusively affecting a lymphoid organ. In 2013, we showed that private deleterious mutations in the protein-coding region of RPSA, encoding ribosomal protein SA, caused ICA by haploinsufficiency with complete penetrance. We reported seven heterozygous protein-coding mutations in 8 of the 23 kindreds studied, including 6 of the 8 multiplex kindreds. We have since enrolled 33 new kindreds, 5 of which are multiplex. We describe here 11 new heterozygous ICA-causing RPSA protein-coding mutations, and the first two mutations in the 5′-UTR of this gene, which disrupt mRNA splicing. Overall, 40 of the 73 ICA patients (55%) and 23 of the 56 kindreds (41%) carry mutations located in translated or untranslated exons of RPSA. Eleven of the 43 kindreds affected by sporadic disease (26%) carry RPSA mutations, whereas 12 of the 13 multiplex kindreds (92%) carry RPSA mutations. We also report that 6 of 18 (33%) protein-coding mutations and the two (100%) 5′-UTR mutations display incomplete penetrance. Three mutations were identified in two independent kindreds, due to a hotspot or a founder effect. Finally, RPSA ICA-causing mutations were demonstrated to be de novo in 7 of the 23 probands. Mutations in RPSA exons can affect the translated or untranslated regions and can underlie ICA with complete or incomplete penetrance
URI: http://hdl.handle.net/10553/48610
ISSN: 0027-8424
DOI: 10.1073/pnas.1805437115
Source: Proceedings of the National Academy of Sciences of the United States of America[ISSN 0027-8424],v. 115, p. E8007-E8016
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