Puel, Anne, Reichenbach, Janine, Bustamante, Jacinta, Ku, Cheng-Lung, Feinberg, Jacqueline, Döffinger, Rainer, Bonnet, Marion ![]() |
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 |
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Date Type: | Publication |
Status: | Published |
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 |
Citation Data
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