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
More filters
Journal ArticleDOI
Role of Drosophila IKK gamma in a toll-independent antibacterial immune response.
Sophie Rutschmann,Alain C. Jung,Rui Zhou,Neal S. Silverman,Jules A. Hoffmann,Dominique Ferrandon +5 more
TL;DR: In this paper, a loss-of-function mutants were generated in the Drosophila homolog of the mammalian I-κB kinase (IKK) complex component IKKγ (also called NEMO), which is required for the Relish-dependent immune induction of the genes encoding antibacterial peptides and resistance to infections by Escherichia coli.
Journal ArticleDOI
Genetics of lymphatic anomalies.
TL;DR: Germline mutations have been identified in at least 20 genes that encode proteins acting around VEGFR-3 signaling but also downstream of other tyrosine kinase receptors that explain more than a quarter of the incidence of primary lymphedema, mostly of inherited forms.
Journal ArticleDOI
Monogenic causes of X-linked mental retardation
Jamel Chelly,Jean-Louis Mandel +1 more
TL;DR: Findings in X-linked genes and proteins affected in three important syndromic forms of XLMR provide important insights into the molecular and cellular defects that underlie mental retardation.
Journal ArticleDOI
Genetic basis of tooth agenesis
TL;DR: The phenotypes associated with mutations in different genes indicate that in addition to an overall reduction of odontogenic potential, tooth class-specific and more complex mechanisms are also involved.
Journal ArticleDOI
Lymphatic System in Cardiovascular Medicine
TL;DR: The most recent advances in the field of lymphatic vascular biology are reviewed, with a focus on cardiovascular disease.
References
More filters
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.
Related Papers (5)
X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappaB signaling.
Rainer Doffinger,Asma Smahi,Christine Bessia,Frederic Geissmann,Jacqueline Feinberg,Anne Durandy,Christine Bodemer,Sue Kenwrick,Sophie Dupuis-Girod,Stéphane Blanche,Philip A. Wood,Smail Hadj Rabia,Denis J. Headon,Paul A. Overbeek,Françoise Le Deist,Steven M. Holland,Kiran Belani,Dinakantha S. Kumararatne,Alain Fischer,Ralph S. Shapiro,Mary Ellen Conley,Eric Reimund,Hermann Kalhoff,Mario Abinun,Arnold Munnich,Alain Israël,Gilles Courtois,Jean-Laurent Casanova +27 more