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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Book ChapterDOI
Delineation of NF-кB Signaling by Gene Targeting
TL;DR: Ghosh et al. as discussed by the authors showed that IкB proteins mask the nuclear localization signal of NF-кB, preventing its translocation to the nucleus, and then they become targets for ubiquitination and proteosome-mediated degradation.
Incontinentia Pigmenti Associated with Seizures: A Case Report and Literature Review
TL;DR: It is suggested that brain destruction of IP can develop even antenatally and seizure can attack after then, and further studies are needed for precise mechanism of CNS anomalies in IP.
Posted ContentDOI
NEMO reshapes the protein aggregate interface and promotes aggrephagy by co-condensation with p62
Nikolas Furthmann,Lena Angersbach,Verian Bader,Alina Blusch,Simran Goel,Ana Sánchez-Vicente,Laura Jasmin Krause,Prerna Grover,Victoria A. Trinkaus,Eva M van Well,Maximilian Jaugstetter,Rune Busk Damgaard,Carsten Saft,Gisa Ellrichmann,Ralf Gold,Arend Koch,B. Englert,Markus Glatzel,F. Ulrich Hartl,Ken Nakamura,Chadwick W. Christine,Eric J. Huang,Jörg Tatzelt,Konstanze F. Winklhofer +23 more
TL;DR: In this article , the authors identified an NF-κB-independent function of NEMO in proteostasis regulation by promoting autophagosomal clearance of protein aggregates, which is a ubiquitin-binding protein which regulates canonical NFκB pathway activation in innate immune signaling, cell death regulation and host-pathogen interactions.
Journal ArticleDOI
Dental findings and management in a child with hypomelanosis of Ito
TL;DR: The oral management and novel dental findings of a male HI patient aged 3 years and 10 months were reported, with the chief complaint was spontaneous gingival bleeding due toGingival hyperplasia induced by anticonvulsants, which was improved with plaque control and gedival massage.
Journal ArticleDOI
Gene table: Monogenic determined neurocutaneous disorders
TL;DR: This work presents very concise review of molecular background of monogenic determined neurocutaneous disorders.
References
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Journal ArticleDOI
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Shoji Yamaoka,Gilles Courtois,Christine Bessia,Simon T. Whiteside,Robert Weil,Fabrice Agou,Heather Kirk,Robert J. Kay,Alain Israël +8 more
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Requirement for NF-κB in osteoclast and B-cell development
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