CINECA IRIS Institutional Research Information System
IRIS è il sistema di gestione integrata dei dati della ricerca (persone, progetti, pubblicazioni, attività) adottato dall'Università degli Studi di Torino.
AperTO è l'archivio istituzionale Open Access destinato a raccogliere, rendere visibile e conservare la produzione scientifica dell'Università degli Studi di Torino.
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 |
File in questo prodotto:
| File | Descrizione | Tipologia | Licenza | |
|---|---|---|---|---|
| NEMO.pdf | 1 Ver. finale autore | Accesso riservato | Utenti riconosciuti Richiedi una copia |
Copyright © 2019