Insight into IKBKG/NEMO locus: report of new mutations and complex genomic rearrangements leading to incontinentia pigmenti disease

Human Mutation
Matilde Immacolata ConteMatilde Valeria Ursini

Abstract

Incontinentia pigmenti (IP) is an X-linked-dominant Mendelian disorder caused by mutation in the IKBKG/NEMO gene, encoding for NEMO/IKKgamma, a regulatory protein of nuclear factor kappaB (NF-kB) signaling. In more than 80% of cases, IP is due to recurrent or nonrecurrent deletions causing loss-of-function (LoF) of NEMO/IKKgamma. We review how the local architecture of the IKBKG/NEMO locus with segmental duplication and a high frequency of repetitive elements favor de novo aberrant recombination through different mechanisms producing genomic microdeletion. We report here a new microindel (c.436_471delinsT, p.Val146X) arising through a DNA-replication-repair fork-stalling-and-template-switching and microhomology-mediated-end-joining mechanism in a sporadic IP case. The LoF mutations of IKBKG/NEMO leading to IP include small insertions/deletions (indel) causing frameshift and premature stop codons, which account for 10% of cases. We here present 21 point mutations previously unreported, which further extend the spectrum of pathologic variants: 14/21 predict LoF because of premature stop codon (6/14) or frameshift (8/14), whereas 7/21 predict a partial loss of NEMO/IKKgamma activity (two splicing and five missense). We review how ...Continue Reading

References

Jan 1, 1993·Journal of Medical Genetics·S J Landy, D Donnai
Aug 1, 1996·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·G Martini, M V Ursini
Jul 27, 2000·Molecular Cell·M Schmidt-SupprianM Pasparakis
Oct 13, 2001·Trends in Molecular Medicine·G CourtoisA Israël
Oct 24, 2001·American Journal of Human Genetics·S KenwrickUNKNOWN International IP Consortium
Jun 26, 2003·Nucleic Acids Research·Michael Zuker
Sep 17, 2003·Archives of Dermatology·Smaïl Hadj-RabiaChristine Bodemer
Oct 28, 2003·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Hao Wu, Joseph R Arron
May 18, 2004·Current Opinion in Cell Biology·Kristian E Baker, Roy Parker
Sep 17, 2004·Genes & Development·Matthew S Hayden, Sankar Ghosh
May 2, 2006·Current Opinion in Genetics & Development·David L Nelson
Jul 18, 2006·Nucleic Acids Research·Oleg KikinParamjeet S Bagga
Aug 4, 2006·The Journal of Clinical Investigation·Athanasios StratisIngo Haase
Sep 13, 2006·Biochemical Pharmacology·Hélène Sebban, Gilles Courtois
Sep 22, 2006·Trends in Cell Biology·Hélène SebbanGilles Courtois
Jan 17, 2007·Journal of the American Academy of Dermatology·Francesca FuscoMatilde Valeria Ursini
May 9, 2007·Frontiers in Bioscience : a Journal and Virtual Library·Kirill S LobachevVidhya Narayanan
May 12, 2007·Trends in Biochemical Sciences·Robert D Wells
Sep 12, 2007·Nature Reviews. Genetics·Jian-Min ChenGeorge P Patrinos
Jan 8, 2008·Lancet·M D Cappellini, G Fiorelli
Mar 20, 2008·Human Mutation·Francesca FuscoMatilde Valeria Ursini
Feb 3, 2009·Molecular Cell·Yu-Chih LoHao Wu
Apr 21, 2009·Nature Genetics·Patrick S TarpeyMichael R Stratton
Jun 6, 2009·Annual Review of Biochemistry·Brian SkaugZhijian J Chen

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Citations

Jun 26, 2014·Orphanet Journal of Rare Diseases·Francesca FuscoMatilde Valeria Ursini
Aug 27, 2015·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Giuliana GiardinoClaudio Pignata
Dec 3, 2015·Cytokine·Christopher P Dillon, Siddharth Balachandran
Jun 27, 2015·Ophthalmic Surgery, Lasers & Imaging Retina·Christian C SwinneyPeter A Karth
Dec 27, 2015·Seminars in Pediatric Neurology·Martino Ruggieri, Andrea D Praticò
Mar 4, 2015·The Journal of Investigative Dermatology·Qiaoli LiJouni Uitto
May 7, 2015·American Journal of Medical Genetics. Part a·Sarah HullAnthony T Moore
Jul 27, 2015·Immunology and Allergy Clinics of North America·Elisabeth de GraauwDagmar Simon
Nov 30, 2014·Cellular and Molecular Life Sciences : CMLS·Anna SenegasGilles Courtois
May 10, 2017·The Journal of Allergy and Clinical Immunology·Glynis FransXavier Bossuyt
Jun 2, 2018·International Journal of Dermatology·Julia Reyes-RealiGlustein Pozo-Molina
Aug 29, 2018·American Journal of Medical Genetics. Part a·Luiza M MariathLavínia Schuler-Faccini
Mar 10, 2018·The Australasian Journal of Dermatology·Sorina DanescuAdrian Baican
Dec 6, 2018·Topics in Magnetic Resonance Imaging : TMRI·Felipe S BarrosBruno P Soares
Nov 14, 2018·The Journal of Clinical Investigation·Bertrand BoissonTakahiro Yasumi
Jul 11, 2019·European Journal of Human Genetics : EJHG·Francesca FuscoMatilde Valeria Ursini
Apr 16, 2020·Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG·Sonja SennerAndreas Wollenberg
Apr 16, 2020·Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG·Sonja SennerAndreas Wollenberg
Jul 18, 2020·Journal of the European Academy of Dermatology and Venereology : JEADV·C BodemerJ Steffann
Jul 15, 2015·Current Opinion in Pediatrics·Jennifer L Hand

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