title: Molecular background and genotype-phenotype correlation in autoimmune-polyendocrinopathy-candidiasis-ectodermal-distrophy patients from Campania and in their relatives.
abstract: 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, 3 hot spots areas where APECED shows an increased prevalence, have been identified in Sardinia, Apulia, and in the Venetian region.
  
  
  OBJECTIVE
  In this study, we analyzed AIRE mutations and genotype-phenotype correlation in APECED patients originating from Campania and in their relatives.
  
  
  METHODS
  In 6 patients affected with APECED clinical findings, genetic analysis of AIRE, and APECED-related autoantibodies were performed.
  
  
  RESULTS
  All patients carried at least 1 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; 2 patients were compound heterozygous for [T16M]+[W78R] (exons 1+2); 1 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.
authors.affiliation: Department of Pediatrics, University "Federico II" of Naples, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Capalbo
authors.forename: C
authors.initials: C
authors.lastname: Mazza
authors.forename: R
authors.initials: R
authors.lastname: Giordano
authors.forename: N
authors.initials: N
authors.lastname: Improda
authors.forename: E
authors.initials: E
authors.lastname: Arvat
authors.forename: S
authors.initials: S
authors.lastname: Cervato
authors.forename: L
authors.initials: L
authors.lastname: Morlin
authors.forename: C
authors.initials: C
authors.lastname: Pignata
authors.forename: C
authors.initials: C
authors.lastname: Betterle
authors.forename: M
authors.initials: M
authors.lastname: Salerno
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D016884:Polyendocrinopathies, Autoimmune / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics; D000096927:AIRE Protein
chemical_list: D014157:Transcription Factors; D000096927:AIRE Protein