Is there a correlation between genotype and phenotype in APECED syndrome? Mutational and clinical analysis of two Turkish families

Abstract

Aim: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene, mapping to 21q22.3. In our study, we aimed to evaluate the AIRE gene mutations in patients with APECED syndrome and in their relatives. Materials and Methods: We investigated the presence of mutation in 2 Turkish families with APECED syndrome, in which the index case of 1 family (patient 1) was clinically complete and the other (patient 2) incomplete. After informed consent was obtained, we performed mutation analysis by sequencing all the 14 exons and the intron-exon boundaries of the AIRE gene on the DNA extracted from the peripheral blood. Results: As a result of AIRE gene analysis, it was found that while homozygote was determined in patient 1, the pathogenic mutation c. 769C > T (p.R257X; g.8473C > T), which turns arginine coding codon 257 into a stop codon, was determined in her father and 3 sisters. However, no mutation was found in patient 2 or her family members. Conclusions: Although phenotypic manifestations of the disease vary largely, it is thought that genetic and/or environmental factors contributing to clinical presentation of the disease are determinant. The R257X mutation in exon 6 was discovered in 89% of the alleles of the Finnish patients with APECED; also this mutation was the most frequent one found in other ethnic groups. Although this mutation has been discovered in different ethnic groups, patients with R257X mutation have similar clinical findings. The significance of our cases arises from the fact that this mutation (R257X) is demonstrated in our ethnical group and geographical area for the first time. © TÜBİTAK.