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
Unilateral incontinentia pigmenti in a male infant
Journal ArticleDOI
Entzündliches Stadium der Incontinentia pigmenti (Bloch-Sulzberger-Syndrom)
Anne-Katrin Kortüm,Amanda S. Büchau,B. Assmann,Thomas Ruzicka,Daniela Bruch-Gerharz,U. Orth,Rudolf Kruse +6 more
Journal ArticleDOI
Successful Allogeneic Stem Cell Transplantation in Nuclear Factor-Kappa B Essential Modulator Deficiency Syndrome After Treosulfan-Based Conditioning: A Case Report.
Adrian Martuszewski,Patrycja Paluszkiewicz,Katarzyna Sierżęga-Staykov,Elżbieta Wawrzyniak-Dzierżek,Małgorzata Salamonowicz-Bodzioch,Jowita Frączkiewicz,Małgorzata Janeczko-Czarnecka,Monika Mielcarek-Siedziuk,Mateusz Nowak,Nel Dąbrowska-Leonik,Beata Wolska-Kuśnierz,Katarzyna Gul,Katarzyna Bąbol-Pokora,Wojciech Młynarski,Krzysztof Kałwak,Marek Ussowicz +15 more
TL;DR: Patients with NEMO deficiency syndrome require very complex, multidisciplinary care, and immunodeficiency correction can only be observed as one of the critical points in patient care.
Journal ArticleDOI
Case 1: Seizures and Rashes Do Run in the Family
TL;DR: Under a presumed diagnosis of neonatal seizures, both basic and extended investigations are undertaken, including infectious, metabolic, hematologic, and endocrinologic tests, and the focal seizures worsen, become generalized, and are accompanied by episodes of apnea, deep desaturation, and bradycardia.
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
TL;DR: In this paper, the sensitivity and kinetics of TNF-α-induced apoptosis were shown to be enhanced in a number of cell types expressing a dominant negative IkappaBalpha (Ikappa-BalphaM).
Journal ArticleDOI
Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-kappa B.
TL;DR: Results indicate that RelA controls inducible, but not basal, transcription in NF-κB-regulated pathways, and suggest that tumour necrosis factor-mediated induction of messenger RNAs for IκBα and granulocyte/macrophage colony stimulating factor (GM-CSF) is defective, although basal levels of these transcripts are unaltered.
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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