Mutation analyses of North American APS-1 patients.
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.
Heino
M
M
Institute of Medical Technology, University of Tampere, Finland. mh55012@uta.fi
Scott
H S
HS
Chen
Q
Q
Peterson
P
P
Mäebpää
U
U
Papasavvas
M P
MP
Mittaz
L
L
Barras
C
C
Rossier
C
C
Chrousos
G P
GP
Stratakis
C A
CA
Nagamine
K
K
Kudoh
J
J
Shimizu
N
N
Maclaren
N
N
Antonarakis
S E
SE
Krohn
K
K
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
D014157:Transcription Factors; D000096927:AIRE Protein