MOLECULAR BACKGROUND AND GENOTYPE-PHENOTYPE CORRELATION IN APECED PATIENTS FROM CAMPANIA AND IN THEIR RELATIVES

Background: Autoimmune-Polyendocrinopathy-Candidiasis-Ectodermal-Distrophy (APECED) is a recessive disease, caused by mutations in the AutoImmune REgulator (AIRE) gene. Different mutations are peculiar of particular populations. In Italy three hot spots areas where APECED shows an increased prevalence, have been identified in Sardinia, Apulia and in the Venetian region. Aim: in this study we analyzed AIRE mutations and genotype-phenotype correlation in APECED patients originating from Campania and in their relatives. Patients and methods: in six patients affected with APECED clinical findings, genetic analysis of AIRE and APECED-related autoantibodies were performed. Results: all patients carried at least one mutation on exon 1 or on splice-site flanking exon 1. Two siblings carried a complex homozygous mutation [IVS1 + 1G>C; IVS1 + 5delG] on intron 1; two patients were compound heterozygous for [T16M]+[W78R] (exons 1+2); one patient was compound heterozygous for [A21V]+[C322fs] (exons 1+8) and another was homozygous for [T16M]+[T16M] on exon 1. Expression of the disease showed wide variability while circulating autoantibodies paralleled to phenotype in each patient. Analysis of relatives allowed the identification of 8 heterozygotes. None of heterozygous subjects presented major findings of APECED. Conclusions: mutations localized on exon 1 and the region flanking exon 1 are common in APECED patients originating from Campania. Genotype-phenotype correlation failed to reveal a relationship between detected mutations and clinical expression. Mutations in heterozygosis in AIRE gene are not associated to major findings of APECED.