title: Delineation of the molecular defects in the AIRE gene in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients from Southern Italy.
abstract: In this study, we have carried out molecular analysis of the AIRE (autoimmune regulator) gene in 11 patients (from 8 families) affected by autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, originating from a restricted area of Southern Italy (the Salento peninsula in Puglia). Of the 16 mutant AIRE alleles from the 8 probands studied, 12 carried a missense mutation (W78R in 9, P539L in 2, and P252L in 1), 2 carried the Q358X nonsense mutation, and 2 carried the 1058delT frameshift mutation. All these mutations except the 1058delT are novel. Each of the detected mutations either predicts a premature termination of the protein or results in a nonconservative amino acid change, most likely adversely affecting the function of the protein. The W78R missense mutation is relatively common in these patients, having been detected (in homozygosity or compound heterozygosity) in 6 of the 8 probands tested, indicating the presence of a founder effect. The results of this study contribute to the delineation of the molecular pathology of the AIRE gene and enhance our ability to perform a molecular diagnosis in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients from Southern Italy.
authors.affiliation: Istituto di Ricerca sulle Talassemie e Anemie Mediterranee, Consiglio Nazionale Ricerche, 09121 Cagliari.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Meloni
authors.forename: Roberto
authors.initials: R
authors.lastname: Perniola
authors.forename: Valeria
authors.initials: V
authors.lastname: Faà
authors.forename: Enrico
authors.initials: E
authors.lastname: Corvaglia
authors.forename: Antonio
authors.initials: A
authors.lastname: Cao
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Rosatelli
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D018389:Codon, Nonsense / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics; D006801:Humans; D007558:Italy; D008297:Male; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D010375:Pedigree; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D000096927:AIRE Protein
chemical_list: D018389:Codon, Nonsense; D014157:Transcription Factors; D000096927:AIRE Protein