X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappaB signaling.
作者： Rainer Döffinger , Asma Smahi , Christine Bessia , Frédéric Geissmann , Jacqueline Feinberg
DOI: 10.1038/85837
关键词: EDARADD 、 Edar Receptor 、 Immunodeficiency 、 IKBKG 、 IκB kinase 、 Ectodysplasins 、 Ectodysplasin A receptor 、 Biology 、 Immunology 、 Ectodermal dysplasia
摘要: The molecular basis of X-linked recessive anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) has remained elusive. Here we report hypomorphic mutations in the gene IKBKG 12 males EDA-ID from 8 kindreds, and 2 patients a related hitherto unrecognized syndrome osteopetrosis lymphoedema (OL-EDA-ID). Mutations coding region are associated EDA-ID, stop codon mutations, OL-EDA-ID. encodes NEMO, regulatory subunit IKK (IκB kinase) complex, which is essential for NF-κB signaling. Germline loss-of-function lethal male fetuses. We show that causing OL-EDA-ID impair but do not abolish also ectodysplasin receptor, DL, triggers through NEMO protein, indicating EDA results impaired Finally, abnormal immunity cell responses to lipopolysaccharide, interleukin (IL)-1β, IL-18, TNFα CD154. thus first time abolished signaling humans two syndromes associate specific developmental immunological defects.
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