Insight into IKBKG/NEMO locus: report of new mutations and complex genomic rearrangements leading to Incontinentia pigmenti disease (Articolo in rivista)

Type
Label
  • Insight into IKBKG/NEMO locus: report of new mutations and complex genomic rearrangements leading to Incontinentia pigmenti disease (Articolo in rivista) (literal)
Anno
  • 2014-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1002/humu.22483. (literal)
Alternative label
  • Conte MI, Pescatore A, Paciolla M, Esposito E, Miano MG, Lioi MB, McAleer MA, Giardino G, Pignata C, Irvine AD, Scheuerle AE, Royer G, Hadj-Rabia S, Bodemer C, Bonnefont J-P, Munnich A, Smahi A, Steffann J, Fusco F and Ursini MV (2014)
    Insight into IKBKG/NEMO locus: report of new mutations and complex genomic rearrangements leading to Incontinentia pigmenti disease
    in Human mutation
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Conte MI, Pescatore A, Paciolla M, Esposito E, Miano MG, Lioi MB, McAleer MA, Giardino G, Pignata C, Irvine AD, Scheuerle AE, Royer G, Hadj-Rabia S, Bodemer C, Bonnefont J-P, Munnich A, Smahi A, Steffann J, Fusco F and Ursini MV (literal)
Pagina inizio
  • 165 (literal)
Pagina fine
  • 177 (literal)
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  • Accepted Articles in 2013 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 35 (literal)
Rivista
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  • Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso', IGB-CNR, Naples, Italy University of Basilicata, Potenza, Italy Department of Pediatric Dermatology, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland National Children's Research Centre, Our Lady's Children's Hospital Dublin, Ireland Department of Pediatrics Federico II University, Naples, Italy School of Medicine, Trinity College Dublin, Dublin, Ireland Tesserae Genetics Dallas, Texas, USA Department of Genetics, INSERM U781, Hôpital Necker-Enfants Malades, Paris, France (literal)
Titolo
  • Insight into IKBKG/NEMO locus: report of new mutations and complex genomic rearrangements leading to Incontinentia pigmenti disease (literal)
Abstract
  • Incontinentia Pigmenti (IP) is an X-linked-dominant Mendelian disorder caused by mutation in the IKBKG/NEMO gene, encoding for NEMO/IKKgamma, a regulatory protein of NF-kB signaling. In more than 80% of cases, IP is due to recurrent or non-recurrent deletions causing Loss-of-Function (LoF) of NEMO/IKKgamma. We review how the local architecture of the IKBKG/NEMO locus with segmental duplication and a high frequency of repetitive elements favor de novo aberrant recombination through different mechanisms producing genomic microdeletion. We report here a new micro-indel (c.436_471delinsT, p.Val146X) arising through a DNA-replication-repair Fork-Stalling-and-Template-Switching (FoSTeS) and Microhomology-Mediated-End-Joining (MMEJ) mechanism in a sporadic IP case. The LoF mutations of IKBKG/NEMO leading to IP include small insertions/deletions (indel) causing frameshift and premature stop codons, which account for 10% of cases. We here present 21 point mutations previously unreported, which further extend the spectrum of pathologic variants: 14/21 predict LoF because of premature stop codon (6/14) or frameshift (8/14), while 7/21 predict a partial loss of NEMO/IKKgamma activity (2 splicing and 5 missense). We review how the analysis of IP-associated IKBKG/NEMO hypomorphic mutants has contributed to the understanding of the pathophysiological mechanism of IP-disease and has provided important information on affected NF-kB signaling. We built a locus-specific database listing all IKBKG/NEMO variants, (literal)
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