APECED mutations in the autoimmune regulator (AIRE) gene

Autoimmune polyendocrinopathy candidiasis,ectodermal dystrophy (APECED) is a rare recessively inherited disorder caused by mutations in the AIRE (auto immune regulator) gene. APECED is characterized by variable combinations of endocrine autoimmune diseases such as Addison's disease, hypoparathyroidis m, and type 1 diabetes. The AIRE protein contains motifs suggestive of a tr anscription regulator and can activate transcription of a reporter gene whe n fused to a heterologous DNA biding domain. In this article, mutation anal yses of over 200 APECED patients published by several laboratories are summ arized. To date 42 different mutations have been identified. These mutation s include nonsense and missense mutations, small insertions and deletions l eading into frame shifts, and splice site mutations. Although mutations are spread throughout the coding region of the gene some hotspots emerge, incl uding the more common and recurrent mutations R257X and 967-979del13bp. Som e of the identified mutations have been shown to affect subcellular localiz ation or transactivation properties of the protein, thus providing insights into the functional properties of the predicted protein motifs. Hum Mutat 18:205-211, 2001. (C) 2001 Wiley-Liss, Inc.