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
Citations
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Journal ArticleDOI
Anaesthesia and orphan disease: A child with incontinentia pigmenti.
TL;DR: In summary, multiple systems and organs are affected in NCL; therefore, they require close monitoring during anaesthesia to rapidly detect and correct problems and the lack of postoperative temperature monitoring may be the cause of the delayed recovery.
Journal ArticleDOI
Incontinencia pigmentaria
TL;DR: Afectación neurooftalmológica provoca las complicaciones más graves, e.g., incontinencia pigmentaria, a enfermedad infrecuente causada by un defecto del gen IKBKG (también conocido con el nombre de NEMO) as mentioned in this paper .
Book ChapterDOI
NF-кB in Genetic Disorders
G. Courtois,A. Israël +1 more
TL;DR: The key role of this protein in activating the NF-кB pathway is demonstrated, as NEMO/IKKγ exhibits no catalytic properties, but acts as a regulatory subunit of IKK.
Journal ArticleDOI
The Impact of the IKBKG Gene on the Appearance of the Corpus Callosum Abnormalities in Incontinentia Pigmenti
Snežana Minić,Natasa Cerovac,Ivana Novakovic,Slobodan Gazikalovic,Svetlana Popadić,Dušan Trpinac +5 more
TL;DR: In this article , the authors examined the IKBKG gene and the X-chromosome inactivation pattern to determine the presence of corpus callosum (CC) abnormalities in Continentia pigmenti (IP).
Journal ArticleDOI
Innate and adaptive immune abnormalities underlying autoimmune diseases: the genetic connections
TL;DR: In this paper , a review of the etiology and pathogenesis of common autoimmune disorders from the perspective of human genetics is presented, with an overview of the genetic basis of autoimmunity followed by three chapters detailing susceptibility genes involved in innate immunity, adaptive immunity and inflammatory cell death processes respectively.
References
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Journal ArticleDOI
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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