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The NEMO mutation creating the most-upstream premature stop codon is hypomorphic because of a reinitiation of translation.

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.
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https://www.hal.inserm.fr/inserm-00142391
Contributor : Nicole Pinhas <>
Submitted on : Wednesday, April 18, 2007 - 4:31:47 PM
Last modification on : Wednesday, August 19, 2020 - 11:16:44 AM

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Anne Puel, Janine Reichenbach, Jacinta Bustamante, Cheng-Lung Ku, Jacqueline Feinberg, et al.. The NEMO mutation creating the most-upstream premature stop codon is hypomorphic because of a reinitiation of translation.. American Journal of Human Genetics, Elsevier (Cell Press), 2006, 78 (4), pp.691-701. ⟨10.1086/501532⟩. ⟨inserm-00142391⟩

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