Nature Genetics
17, 399 - 403 (1997)
doi:10.1038/ng1297-399
An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domainsJohanna Aaltonen1, Petra Björses1, Jaakko Perheentupa2, Nina Horelli−Kuitunen3, Aarno Palotie3, Leena Peltonen1, Yeon Su Lee4, Fiona Francis4, Steffen Henning4, Cora Thiel4, Hans Leharach4
& Marie−Laure Yaspo4
1Department of Human Molecular Genetics, Institute of Biomedicine, University of Helsinki and National Public Health Institute, Mannerheimintie 166, Fin-00300 Helsinki, Finland.
2Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland.
3Department of Clinical Chemistry and Biomedicine, Unversity of Helsinki, Helsinki, Finland.
4Max Planck Institute for Molecular Genetics, Ihnestrasse 73, D-14195 Berlin, Germany.
5J.A. and P.B. contributed equally to this work.
6e-mail: leena.peltonen@ktl.fi or yaspo@mpimg-berlin-dahlem.mpg.de
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is the only described systemic autoimmune disease with established monogenic background, and the first autoimmune disorder localized outside the major histocompatibility complex (MHC) region. The primary biochemical defect in APECED is unknown. We have isolated a novel gene, AIRE, encoding for a putative nuclear protein featuring two PHD-type zinc-finger motifs, suggesting its involvement in transcriptional regulation. Five mutations in AIRE are reported in individuals with this disorder. This is the first report of a single-gene defect causing a systemic human autoimmune disease, providing a tool for exploring the molecular basis of autoimmunity.
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