Puel, Anne, Reichenbach, Janine, Bustamante, Jacinta, Ku, Cheng-Lung, Feinberg, Jacqueline, Döffinger, Rainer, Bonnet, Marion  ORCID: https://orcid.org/0000-0002-7559-2413, Filipe-Santos, Orchidée, de Beaucoudrey, Ludovic, Durandy, Anne, Horneff, Gerd, Novelli, Francesco, Wahn, Volker, Smahi, Asma, Israel, Alain, Niehues, Tim and Casanova, Jean-Laurent
2006.
The NEMO mutation creating the most-upstream premature stop codon is hypomorphic because of a reinitiation of translation.
American Journal of Human Genetics
78
(4)
, pp. 691-701.
10.1086/501532
|
Abstract
Amorphic mutations in the NF-κB essential modulator (NEMO) cause X-dominant incontinentia pigmenti, which is lethal in males in utero, whereas hypomorphic mutations cause X-recessive anhidrotic ectodermal dysplasia with immunodeficiency, a complex developmental disorder and life-threatening primary immunodeficiency. We characterized the NEMO mutation 110_111insC, which creates the most-upstream premature translation termination codon (at codon position 49) of any known NEMO mutation. Surprisingly, this mutation is associated with a pure immunodeficiency. We solve this paradox by showing that a Kozakian methionine codon located immediately downstream from the insertion allows the reinitiation of translation. The residual production of an NH2-truncated NEMO protein was sufficient for normal fetal development and for the subsequent normal development of skin appendages but was insufficient for the development of protective immune responses.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Medicine |
| Publisher: | Elsevier (Cell Press) |
| ISSN: | 0002-9297 |
| Date of First Compliant Deposit: | 17 February 2021 |
| Date of Acceptance: | 13 January 2006 |
| Last Modified: | 09 Nov 2022 10:11 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/138623 |
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