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Novel AIRE mutations and P450 cytochrome autoantibodies in Central and Eastern European patients with APECED
Author(s) -
Cihakova Daniela,
Trebusak Katarina,
Heino Maarit,
Fadeyev Valentin,
Tiulpakov Anatoly,
Battelino Tadej,
Tar Attila,
Halász Zita,
Blümel Peter,
Tawfik Sameh,
Krohn Kai,
Lebl Jan,
Peterson Pärt
Publication year - 2001
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.1178
Subject(s) - autoimmune regulator , autoantibody , biology , vitiligo , genetics , immunology , autoimmunity , mutation , gene , antibody
Autoimmune polyendocrinopathy‐candidiasis‐ectodermal dystrophy (APECED) is a rare recessive disorder that results in several autoimmune diseases due to the mutations in the AIRE (autoimmune regulator) gene. APECED patients develop several autoimmune endocrine disorders and are characterized by the high titer autoantibodies to organ‐specific antigens such as the steroidogenic P450 cytochromes. So far, 38 mutations have been identified in the AIRE gene. We report here the genetic and autoantibody analysis of 27 APECED patients of Eastern and Central European origins and one Egyptian patient. From 54 analyzed APECED chromosomes, eight mutations were detected, four of which (T16M, W78R, IVS1_IVS4, 30–53dup23bp) are novel. The most prevalent reason for APECED in these populations was the occurrence of R257X (36 chromosomes) that has been described earlier as a common and recurrent mutation in several other populations. The analysis of humoral immunity to steroidogenic 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 Central European APECED patients had autoantibodies to P450c17, P450c21, and P450scc, respectively. Hum Mutat 18:225–232, 2001. © 2001 Wiley‐Liss, Inc.