title: Detection of a complete autoimmune regulator gene deletion and two additional novel mutations in a cohort of patients with atypical phenotypic variants of autoimmune polyglandular syndrome type 1.
abstract: OBJECTIVE
  Autoimmune polyglandular syndrome type 1 (APS-1) is characterised by multiple autoimmune diseases. Detection of autoimmune regulator (AIRE) gene mutations facilitates timely and precise diagnosis.
  
  
  METHODS
  AIRE mutation detection was performed in a cohort of 11 patients. Two did not meet clinical APS-1 criteria and several started with atypical presentation.
  
  
  METHODS
  Sequencing and TaqMan genotyping were used to identify AIRE mutations. Complete AIRE deletion was confirmed and framed by real-time PCR, long-range amplification and analysis of the microsatellite markers.
  
  
  RESULTS
  Seven different mutations were detected, three were novel: c.892G>A in exon 8, silent mutation c.462A>T in exon 3 most likely affecting splicing, and a complete deletion of a single AIRE allele ((?_68)_(1567-14_?)del). Novel (chronic otitis) and rare (systemic juvenile rheumatoid arthritis, autoimmune bronchiolitis, epilepsy) clinical presentations were observed.
  
  
  CONCLUSIONS
  AIRE mutation detection was valuable in the diagnostics of APS-1 in patients with atypical presentation. Chronic otitis media possibly broadened the cluster of APS-1 manifestations.
authors.affiliation: Centre for Medical Genetics, University Medical Centre, University Children's Hospital, Ljubljana, Slovenia. katarina.trebusak@kclj.si
authors.forename: Katarina Trebusak
authors.initials: KT
authors.lastname: Podkrajsek
authors.forename: Tatjana
authors.initials: T
authors.lastname: Milenković
authors.forename: Roelof J
authors.initials: RJ
authors.lastname: Odink
authors.forename: Hedi L
authors.initials: HL
authors.lastname: Claasen-van der Grinten
authors.forename: Nina
authors.initials: N
authors.lastname: Bratanic
authors.forename: Tinka
authors.initials: T
authors.lastname: Hovnik
authors.forename: Tadej
authors.initials: T
authors.lastname: Battelino
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D017353:Gene Deletion; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D010641:Phenotype; D017354:Point Mutation; D016884:Polyendocrinopathies, Autoimmune / Q000175:diagnosis / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D000096927:AIRE Protein
chemical_list: D014157:Transcription Factors; D000096927:AIRE Protein