AN AUTOIMMUNE-DISEASE, APECED, CAUSED BY MUTATIONS IN A NOVEL GENE FEATURING 2 PHD-TYPE ZINC-FINGER DOMAINS

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED ) is the only described systemic autoimmune disease with established m onogenic background, and the first autoimmune disorder localized outsi de the major histocompatibility complex (MHC) region. The primary bioc hemical defect in APECED is unknown. We have isolated a novel gene, AI RE, encoding for a putative nuclear protein featuring two PHD-type zin c-finger motifs, suggesting its involvement in transcriptional regulat ion. Five mutations in AIRE are reported in individuals with this diso rder. This is the first report of a single-gene defect causing a syste mic human autoimmune disease, providing a tool for exploring the molec ular basis of autoimmunity.