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

American Journal of Human Genetics
Anne PuelJean-Laurent Casanova

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.

References

Aug 3, 2001·American Journal of Human Genetics·K KosakiN Matsuo
Sep 8, 2001·Journal of Medical Genetics·M Priolo, C Laganà
Sep 13, 2002·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Marilyn Kozak
Mar 15, 2003·Science·Capucine PicardJean-Laurent Casanova
Mar 26, 2003·Archives of Disease in Childhood·E D CarrolM Abinun
Jan 22, 2005·Immunological Reviews·Cheng-Lung KuJean-Laurent Casanova
Apr 19, 2005·Pediatrics·Cheng-Lung KuJean-Laurent Casanova

❮ Previous
Next ❯

Citations

Jul 4, 2009·Journal of Clinical Immunology·Asghar AghamohammadiLennart Hammarström
May 28, 2013·Journal of Clinical Immunology·Lena F SchimkeTroy R Torgerson
Mar 8, 2007·European Journal of Human Genetics : EJHG·Angela InácioLuísa Romão
Jul 5, 2006·The Journal of Experimental Medicine·Orchidée Filipe-SantosJean-Laurent Casanova
Oct 8, 2009·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·William R BerringtonCorey Casper
Jul 8, 2011·Clinical Microbiology Reviews·Capucine PicardAnne Puel
Sep 5, 2006·Journal of Medical Genetics·Cheng-Lung KuJean-Laurent Casanova
May 12, 2007·Annual Review of Genomics and Human Genetics·A FortinP Gros
Dec 9, 2008·BMC Genetics·Almoutassem B ZetouneSylvie Mazoyer
Jan 12, 2011·Annual Review of Immunology·Jean-Laurent CasanovaLluis Quintana-Murci
Jan 8, 2013·Current Opinion in Immunology·Shen-Ying ZhangJean-Laurent Casanova
Feb 22, 2012·Current Opinion in Virology·Vanessa Sancho-ShimizuJean-Laurent Casanova
Jul 5, 2011·The Journal of Allergy and Clinical Immunology·Magali AudryAnne Puel
Jun 18, 2010·The Journal of Pediatrics·Laurent AbelMarc Tardieu
Dec 17, 2008·The Journal of Allergy and Clinical Immunology·Saleh Al-Muhsen, Jean-Laurent Casanova
Apr 22, 2008·Immunology and Allergy Clinics of North America·Jacinta BustamanteJean-Laurent Casanova
Jun 15, 2007·Biochimie·Emmanuelle JouanguyJean-Laurent Casanova
Oct 24, 2007·The British Journal of Dermatology·P M SteijlenM A M van Steensel
Mar 20, 2008·Human Mutation·Francesca FuscoMatilde Valeria Ursini
Jan 13, 2012·Annals of the New York Academy of Sciences·Jacinta BustamanteJean-Laurent Casanova
Sep 26, 2006·Seminars in Immunology·Orchidée Filipe-SantosJean-Laurent Casanova
Dec 18, 2007·Current Opinion in Immunology·Jacinta BustamanteJean-Laurent Casanova
Apr 28, 2017·PloS One·Gabriel N Teku, Mauno Vihinen
Mar 6, 2018·Critical Reviews in Clinical Laboratory Sciences·Ana Esteve-SoléJacinta Bustamante
Aug 31, 2017·Annual Review of Genetics·Adam D KenneyJacob S Yount
Nov 14, 2018·The Journal of Clinical Investigation·Bertrand BoissonTakahiro Yasumi
Nov 9, 2007·Current Opinion in Allergy and Clinical Immunology·Vanessa Sancho-ShimizuJean-Laurent Casanova
Dec 24, 2019·PLoS Pathogens·Stéphanie BibertPierre-Yves Bochud
Dec 2, 2015·Proceedings of the National Academy of Sciences of the United States of America·Jean-Laurent Casanova
Jun 10, 2017·Journal of Clinical Immunology·Bertrand BoissonJean-Laurent Casanova

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.