Title: NF-κB signalling requirement for brain myelin formation is shown by genotype/MRI phenotype correlations in patients with Xq28 duplications
Authors: Philippe, Orianne ×
Rio, Marlène
Malan, Valérie
Van Esch, Hilde
Baujat, Geneviève
Bahi-Buisson, Nadia
Valayannopoulos, Vassili
Gesny, Roseline
Bonnefont, Jean-Paul
Munnich, Arnold
Froyen, Guy
Amiel, Jeanne
Boddaert, Nathalie
Colleaux, Laurence #
Issue Date: Feb-2013
Publisher: Karger
Series Title: European Journal of Human Genetics vol:21 issue:2 pages:195-199
Article number: 10.1038/ejhg.2012.140
Abstract: One of the key signals regulating peripheral myelin formation by Schwann cell is the activation of the transcription factor NF-κB. Yet, whether NF-κB exerts similar functions in central myelin formation by oligodendrocytes remains largely unknown. We previously reported white matter abnormalities with unusual discordance between T2 and FLAIR sequences in a patient with intellectual disability and defective NF-κB signalling. These observations prompted us to hypothesise that NF-κB signalling may have a role in the axon myelination process of central neurons. We report here on five male patients with Xq28 duplications encompassing MECP2, three of which presented white matter anomalies on brain MRI. Array-CGH and FISH analyses demonstrated that brain abnormalities correlate with additional copies of the IKBKG, a gene encoding a key regulator of NF-κB activation. Quantitative RT-PCR experiments and κB-responsive reporter gene assays provide evidence that IKBKG overexpression causes impaired NF-κB signalling in skin fibroblasts derived from patients with white matter anomalies. These data further support the role of NF-κB signalling in astroglial cells for normal myelin formation of the central nervous system.European Journal of Human Genetics advance online publication, 18 July 2012; doi:10.1038/ejhg.2012.140.
ISSN: 1018-4813
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Human Genome Laboratory (-)
× corresponding author
# (joint) last author

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