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
Host susceptibility factors in mycobacterial infection: Genetics and body morphotype
TL;DR: Through identification and evaluation of mutations and polymorphisms in components of the IFN gamma response pathways, a better understanding of the mechanisms and risk factors influencing the development of mycobacterial disease is gained, which may lead the way for development of therapeutic and preventative strategies.
Journal ArticleDOI
Identification of TRAF6-dependent NEMO polyubiquitination sites through analysis of a new NEMO mutation causing incontinentia pigmenti
Hélène Sebban-Benin,Alessandra Pescatore,Francesca Fusco,Valérie Pascuale,Jérémie Gautheron,Shoji Yamaoka,Anne Moncla,Matilde Valeria Ursini,Gilles Courtois +8 more
TL;DR: The molecular characterization of a new missense mutation of NEMO (A323P) which causes a severe form of incontinentia pigmenti (OMIM#308300), an inherited disease characterized predominantly by skin inflammation, indicates that post-translational modification of NemO through K63-linked polyubiquitination is a key event in IKK activation and that perturbation of this step may cause human pathophysiology.
Journal ArticleDOI
Clinical diagnosis of incontinentia pigmenti in a cohort of male patients.
TL;DR: Three patients with incontinentia pigmenti showed evidence by polymerase chain reaction analysis of both the normal NEMO gene and the exon 4-10 deletion in NemO that occurs in the majority of affected girls with IP, confirming postzygotic mosaicism for the N EMO gene.
Book
NF-κB-Related Genetic Diseases
G Courtois,A Smahi +1 more
TL;DR: Analysis of these diseases has uncovered new critical roles played by this transcription factor in the development and homeostasis of the epidermis and the proper function of lymphatic vessels, and identified mutations will help understanding at the molecular level how NF-κB is activated in response to cell stimulation.
Journal ArticleDOI
Incontinentia pigmenti: report on data from 2000 to 2013.
Francesca Fusco,Mariateresa Paciolla,Matilde Immacolata Conte,Alessandra Pescatore,Elio Esposito,Peppino Mirabelli,Maria Brigida Lioi,Matilde Valeria Ursini +7 more
TL;DR: The building-up of a database of information related to 386 cases of Incontinentia Pigmenti collected in a thirteen-year activity at the centre of expertise is reported on.
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.
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Suppression of TNF-α-Induced Apoptosis by NF-κB
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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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