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EnglishAmorphic mutations in the NF- kappa B 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 NH(2)-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.
| Titolo: | The NEMO mutation creating the most-upstream premature stop codon is hypomorphic because of a reinitiation of translation | |
| Autori Riconosciuti: | ||
| Autori: | A. PUEL; J. REICHENBACH; J. BUSTAMANTE; C-L. KU; J. FEINBERG; R. DFFINGER; M. BONNET; O. FILIPE SANTOS; L. DE BEAUCOUDREY; A. DURANDY; G. HORNEFF; F. NOVELLI; V. WAHN; A. SMAHI; A. ISRAEL; T. NIEHUES; J.-L. CASANOVA | |
| Data di pubblicazione: | 2006 | |
| Abstract: | Amorphic mutations in the NF- kappa B 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 NH(2)-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. | |
| Volume: | 78 | |
| Pagina iniziale: | 691 | |
| Pagina finale: | 701 | |
| URL: | http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=16532398 | |
| Parole Chiave: | NEMO; NFKB; bacterial infections; immunodeficiency | |
| Rivista: | AMERICAN JOURNAL OF HUMAN GENETICS | |
| Appare nelle tipologie: | 03A-Articolo su Rivista |
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| NEMO.pdf | POSTPRINT (VERSIONE FINALE DELL’AUTORE) | Accesso riservato | Utenti riconosciuti Richiedi una copia |
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