AUTOIMMUNE POLYENDOCRINOPATHY-CANDIDIASIS-ECTODERMAL-DYSTROPHY (APECED) IN SICILY: CONFIRMATION THAT R203X IS THE PECULIAR AIRE GENE MUTATION

Objective: autoimmune polyendocrinopathy-candidiasis-ectodermal-dystrophy (APECED), also known as autoimmune polyendocrine syndrome type 1 (APS-1) (OMIM 240300), is a very rare disease. Accepted criteria for diagnosis require the presence of at least two of three major clinical features: chronic mucocutaneous candidiasis (CMC), chronic hypoparathyroidism (CH) and Addison’s disease (AD). Aim: we analyzed AIRE gene mutations and genotype-phenotype correlation in APECED patients originating from Sicily and in their relatives. Subjects and Methods: in four patients clinical evaluations, genetic analysis of AIRE and APECED-related autoantibodies were performed. Results: two patients carried the mutation R203X in homozygosis on exon 5. One had the mutation R203X combined with R139X. The fourth had the R203X mutation in heterozygosis with R257X. Expression of the disease showed wide variability of clinical manifestations. Analysis of relatives allowed the identification of 10 heterozygotes for AIRE gene mutations. None of these subjects presented major findings of APECED. Three of the four patients were positive for autoantibodies to interferon-omega. Conclusions: in Sicily R203X is confirmed to be the typical recessive and prevalent AIRE gene mutation on exon 5. Genotype-phenotype correlation failed to reveal a relationship between detected mutations and clinical expression. Mutations in heterozygosity in AIRE gene are not associated with major findings of APECED.