Journal ArticleDOI
Genomic rearrangement in NEMO impairs NF-kappaB activation and is a cause of incontinentia pigmenti. The International Incontinentia Pigmenti (IP) Consortium.
A. Smahi,Gilles Courtois,Pierre Vabres,Shoji Yamaoka,S. Heuertz,Arnold Munnich,Alain Israël,Nina S. Heiss,Sabine M. Klauck,Petra Kioschis,Stefan Wiemann,Annemarie Poustka,Teresa Esposito,T. Bardaro,Fernando Gianfrancesco,Alfredo Ciccodicola,Michele D'Urso,Hayley Woffendin,T. Jakins,D. Donnai,H. Stewart,Susan Kenwrick,Swaroop Aradhya,Takanori Yamagata,Michael J. Levy,Richard A. Lewis,David L. Nelson +26 more
TLDR
Most cases of familial incontinentia pigmenti are due to mutations of this locus and that a new genomic rearrangement accounts for 80% of new mutations, which means that NF-κB activation is defective in IP cells.Abstract:
Familial incontinentia pigmenti (IP; MIM 308310) is a genodermatosis that segregates as an X-linked dominant disorder and is usually lethal prenatally in males. In affected females it causes highly variable abnormalities of the skin, hair, nails, teeth, eyes and central nervous system. The prominent skin signs occur in four classic cutaneous stages: perinatal inflammatory vesicles, verrucous patches, a distinctive pattern of hyperpigmentation and dermal scarring. Cells expressing the mutated X chromosome are eliminated selectively around the time of birth, so females with IP exhibit extremely skewed X-inactivation. The reasons for cell death in females and in utero lethality in males are unknown. The locus for IP has been linked genetically to the factor VIII gene in Xq28 (ref. 3). The gene for NEMO (NF-kappaB essential modulator)/IKKgamma (IkappaB kinase-gamma) has been mapped to a position 200 kilobases proximal to the factor VIII locus. NEMO is required for the activation of the transcription factor NF-kappaB and is therefore central to many immune, inflammatory and apoptotic pathways. Here we show that most cases of IP are due to mutations of this locus and that a new genomic rearrangement accounts for 80% of new mutations. As a consequence, NF-kappaB activation is defective in IP cells.read more
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Journal ArticleDOI
A nonsense mutation in IKBKB causes combined immunodeficiency.
Talal Mousallem,Jialong Yang,Thomas J. Urban,Hongxia Wang,Mehdi Adeli,Roberta E. Parrott,Joseph L. Roberts,David Goldstein,Rebecca H. Buckley,Rebecca H. Buckley,Xiao-Ping Zhong,Xiao-Ping Zhong +11 more
TL;DR: Data indicate that mutated IKBKB is the likely cause of immunodeficiency in these 4 patients, which presented at an early age with fungal, viral, and bacterial infections and hypogammaglobulinemia.
Journal ArticleDOI
Incontinentia pigmenti case series: clinical spectrum of incontinentia pigmenti in 53 female patients and their relatives.
TL;DR: It is found that, while the frequency of the first three cutaneous stages of IP was comparable with previous studies, none of the secondary cases manifested any serious neurological complications but all displayed stage IV pale anhidrotic reticulate lines on their posterior calves.
Journal ArticleDOI
Regulation of IκB Kinase (IKK)γ/NEMO Function by IKKβ-mediated Phosphorylation *
TL;DR: The results indicate that the differential phosphorylation of IKKγ/NEMO by IKKβ and perhaps other kinases may be important in regulating IKK activity.
Journal ArticleDOI
Incontinentia pigmenti—ophthalmological observation of a series of cases and review of the literature
TL;DR: An examination schedule for patients with and without retinal pathology is outlined and fluorescein angiography in patients with retina pathology is recommended to fully determine the extent of ischaemia.
Journal ArticleDOI
Tnfa Signaling Through Tnfr2 Protects Skin Against Oxidative Stress–Induced Inflammation
Sergio Candel,Sofia de Oliveira,Sofia de Oliveira,Azucena López-Muñoz,Diana García-Moreno,Raquel Espín-Palazón,Sylwia D. Tyrkalska,Sylwia D. Tyrkalska,María L. Cayuela,Stephen A. Renshaw,Raúl Corbalán-Vélez,Inmaculada Vidal-Abarca,Huai-Jen Tsai,José Meseguer,María P. Sepulcre,Victoriano Mulero +15 more
TL;DR: A new zebrafish model of skin inflammatory disease explains new-onset and worsening psoriasis and lichen planus in patients receiving anti-TNFα therapy.
References
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NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses
TL;DR: Recently, significant advances have been made in elucidating the details of the pathways through which signals are transmitted to the NF-kappa B:I kappa B complex in the cytosol and their implications for the study of NF-Kappa B.
Journal ArticleDOI
Suppression of TNF-α-Induced Apoptosis by NF-κB
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Journal ArticleDOI
Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-kappa B.
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Journal ArticleDOI
Complementation Cloning of NEMO, a Component of the IκB Kinase Complex Essential for NF-κB Activation
Shoji Yamaoka,Gilles Courtois,Christine Bessia,Simon T. Whiteside,Robert Weil,Fabrice Agou,Heather Kirk,Robert J. Kay,Alain Israël +8 more
TL;DR: A flat cellular variant of HTLV-1 Tax-transformed rat fibroblasts, 5R, which is unresponsive to all tested NF-κB activating stimuli is characterized, and its genetic complementation is reported.
Journal ArticleDOI
Requirement for NF-κB in osteoclast and B-cell development
Guido Franzoso,Louise Carlson,Lianping Xing,Ljiljana Poljak,Elizabeth W. Shores,Keith Brown,Antonio Leonardi,Tom Tran,Brendan F. Boyce,Ulrich Siebenlist +9 more
TL;DR: It is demonstrated that unlike the respective single knockout mice, the p50/p52 double knockout mice fail to generate mature osteoclasts and B cells, apparently because of defects that track with these lineages in adoptive transfer experiments.
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