Dysfunctional NF-andkappa;B and brain myelin formation

摘要

In a recent issue of the European Journal of Human Genetics, Philippe et al reported on a duplication of the Xq28 locus and its supposed contribution to distorted brain myelination in patients carrying this mutation. They provided evidence that additional copies of the IKBKG gene (encoding NEMO, the regulatory subunit of the IKK complex) functionally impair NF-kB signaling, which in turn leads to the developmental brain abnormalities and mild mental retardation. MRI-based application of axial T_2-weighted FSE and coronal FLAIR sequences to differentiate between CNS white and gray matter confirmed defective myelination in three out of five patients. The authors also presented convincing data that, as exemplified by isolated fibroblasts, NF-kappaB-dependent gene expression is indeed unpaired in these patients carrying the IKBKG mutation. Accounting for the structural phenotype observed, they concluded that proper myelination requires NF-kB activation in CNS-intrinsic cell populations.