THE GENETIC IP DEFECTS: MOLECULAR ANALYSIS OF NEMO GENE AND OTHER NF-kB RELATED GENES

In collaboration with International IP Consortium we recently demonstrated that 78% of patients of Incontinentia Pigmenti (IP; MIM 308310) show amorphic mutations in NEMO/IKKg gene (NF-kB Essential MOdulator). The complete loss of NF-kB activation is lethal for males during embryogenesis but females can survive, owing to mosaicism as a result of X-inactivation. Moreover, it has been reported that hypomorphic mutations in the NEMO gene lead to a Ectodermal Dysplasia, Hypohidrotic with Immunodeficiency (ED-ID; MIM 300291). In human, these mutations affecting NEMO gene impair but do not abolish NF-kB signaling resulting in two related syndromes that associate specific developmental and immunological defects. The goal of the present proposal is to assess the molecular defect in those 23% of IP and ED-ID patients who show no mutations in NEMO coding regions, by looking for sequence alterations in the NEMO gene promoters. In the main time, new genes will be identified trought the comparison of gene expression profiles in IP, ED-ID and EDA which will be considered and processed as candidate for both IP and other EDs with immunodeficiency.