title: Mutation analyses of North American APS-1 patients.
abstract: Autoimmune polyendocrinopathy syndrome type 1 (APS-1; MIM# 240300) is a rare autosomal recessively inherited disease characterised by destructive autoimmune diseases of endocrine glands. The gene responsible for APS-1, known as AIRE (for autoimmune regulator), was recently identified and contains motifs suggestive of a transcription regulator. To date, nine APS-1-associated mutations have been identified in the AIRE gene, including two common mutations R257X and 1094-1106del. In addition to these two mutations, we report seven novel mutations in 16 APS-1 patients from North America. We found that 1094-1106del and R257X were the most common mutations in this population of mixed geoethnic origin, accounting for 17/32 and 4/32 alleles, respectively. Haplotype analyses suggest that both are recurrent mutations, occurring on several different haplotypes with closely linked markers. All the novel mutations appear to be rare, occurring in only single APS-1 families. After examining all coding sequences and exon/intron boundaries of the AIRE gene, the other APS-1 allele remained unidentified in three patients. Genotype-phenotype correlations for APS-1 remain difficult, suggesting that other genetic or environmental factors, or both, influence the clinical presentation and disease progression in individual APS-1 patients.
authors.affiliation: Institute of Medical Technology, University of Tampere, Finland. mh55012@uta.fi
authors.forename: M
authors.initials: M
authors.lastname: Heino
authors.forename: H S
authors.initials: HS
authors.lastname: Scott
authors.forename: Q
authors.initials: Q
authors.lastname: Chen
authors.forename: P
authors.initials: P
authors.lastname: Peterson
authors.forename: U
authors.initials: U
authors.lastname: Mäebpää
authors.forename: M P
authors.initials: MP
authors.lastname: Papasavvas
authors.forename: L
authors.initials: L
authors.lastname: Mittaz
authors.forename: C
authors.initials: C
authors.lastname: Barras
authors.forename: C
authors.initials: C
authors.lastname: Rossier
authors.forename: G P
authors.initials: GP
authors.lastname: Chrousos
authors.forename: C A
authors.initials: CA
authors.lastname: Stratakis
authors.forename: K
authors.initials: K
authors.lastname: Nagamine
authors.forename: J
authors.initials: J
authors.lastname: Kudoh
authors.forename: N
authors.initials: N
authors.lastname: Shimizu
authors.forename: N
authors.initials: N
authors.lastname: Maclaren
authors.forename: S E
authors.initials: SE
authors.lastname: Antonarakis
authors.forename: K
authors.initials: K
authors.lastname: Krohn
mesh_terms: D004252:DNA Mutational Analysis; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006238:Haploidy; D006801:Humans; D008297:Male; D009656:North America / Q000208:ethnology; D010641:Phenotype; D016884:Polyendocrinopathies, Autoimmune / Q000208:ethnology / Q000235:genetics*; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics*; D000096927:AIRE Protein
chemical_list: D014157:Transcription Factors; D000096927:AIRE Protein