Anhidrotic Ectodermal Dysplasia with Immunodeficiency (EDA-ID), X-linked
X-linked recessive EDA-ID (OMIM # 300291) is an immune deficiency with hypohidrotic ectodermal dysplasia caused by hypomorphic hemizygous mutations in IKBKG which encodes IKK-gamma/NF-kappa-B essential modulator (NEMO).
The NF-B signaling cascade is comprised of transcription factors that are normally sequestered in an inactive state in the cytoplasm. They are held in an inactive state through their interaction with IkB inhibitors. In response to a variety of immune and inflammatory stimuli, the IkB molecules become phosphorylated by an IkB kinase (IKK) core complex on two critical serine residues. This is a prerequisite to recognition by UBE2D3 leading to polyubiquitination and subsequent proteasomal degradation. This releases the NF-kB transcription factors and allows them to translocate into the nucleus where they initiate distinct profiles of gene expression depending on the cell...
- Vinolo E, Sebban H, Chaffotte A, et al. A point mutation in NEMO associated with anhidrotic ectodermal dysplasia with immunodeficiency pathology results in destabilization of the oligomer and reduces lipopolysaccharide and tumor necrosis factor-mediated NF-kappa B activation. J Biol Chem. 2006;281(10):6334–48.CrossRefGoogle Scholar