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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Book ChapterDOI
Hypohidrotic Ectodermal Dysplasia (HED)
TL;DR: The broader definition endeavouring all ectodermal derived structures, according to a recent review, has definite benefits in that the problems encountered by many patients and families are similar regardless of the specific subtype of ED.
Journal Article
A Case of Gastric Rupture in Non-Neonatal Child with Incontinentia Pigmenti and Intestinal Neuronal Dysplasia, is there any Correlation?
Ester De Luca,Debora De Bartolo,Natalia Minelli,Francesco Ausania,Santo Gratteri,Pietrantonio Ricci +5 more
TL;DR: A case of 6 year old girl who sustained sudden and lethal gastric rupture, affected by Incontinentia Pigmenti (IP), a genetic disease, is reported, on the basis of clinical and histological findings, that it has determined an increase of pressure at gastrointestinal level, with serious stomach distension until fatal Gastric rupture.
Journal ArticleDOI
Incontinencia pigmenti con defecto en la inmunidad celular
Antonio Zamora-Chávez,Argelia Escobar-Sánchez,Stanislaw Sadowinski-Pine,Omar Josué Saucedo-Ramírez,Palmira Delgado-Barrera,Claudia G. Enríquez-Quiñones +5 more
TL;DR: Incontinentia pigmenti affects all ectodermderived tissues such as skin, appendages, eyes, teeth and central nervous system as well as disorders of varying degree of cellular immunity characterized by decreasing melanin in the epidermis and increase in the dermis.
Journal ArticleDOI
Genetic mutation in male patients with incontinentia pigmenti
TL;DR: It is reported that no NEMO mutation was detected in the male patient with typical linear vesicles as a newborn, streaks of hypopigmentation at 2 months of age, typical vesicle histology and normal 46, XY karyotype, which is similar to the detection rates in the literature.
Journal ArticleDOI
Inherited proliferative vitreoretinopathies of childhood.
TL;DR: There are a number of inherited, childhood disorders of the retinal vasculature that result in vitreoretinal proliferation, and these include familial exudative Vitreoretinopathy (FEVR), Norrie disease (ND), incontinentia pigmenti (IP), autosomal dominant neovascular inflammatory vitre theoreticopathy (ADNI).
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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