Novel AIRE mutations and P450 cytochrome autoantibodies in Central and Eastern European patients with APECED

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare recessive disorder that results in several autoimmune diseases due t o the mutations in the AIRE (autoimmune regulator) gene. APECED patients de velop several autoimmune endocrine disorders and are characterized by the h igh titer autoantibodies to organ-specific antigens such as the steroidogen ic P450 cytochromes. So far, 38 mutations have been identified in the AIRE gene. We report here the genetic and autoantibody analysis of 27 APECED pat ients of Eastern and Central European origins and one Egyptian patient. Fro m 54 analyzed APECED chromosomes, eight mutations were detected, four of wh ich (T16M, W78R, IVS1_IVS4, 30-53dup23bp) are novel. The most prevalent rea son for APECED in these populations was the occurrence of R257X (36 chromos omes) that has been described earlier as a common and recurrent mutation in several other populations. The analysis of humoral immunity to steroidogen ic P450 cytochromes by the immunoblotting of E. coli expressed antigens in the 18 APECED patients showed that 67%, 44%, and 61% of the Eastern and Cen tral European APECED patients had autoantibodies to P450c17, P450c21, and P 450scc, respectively. Hum Mutat 18:225-232, 2001. (C) 2001 Wiley-Liss, Inc.