Mutation analyses of North American APS-1 patients

Autoimmune polyendocrinopathy syndrome type 1 (APS-1; MIM# 240300) is a rar e autosomal recessively inherited disease characterised by destructive auto immune diseases of endocrine glands. The gene responsible for APS-1, known as AIRE (for autoimmune regulator), was recently identified and contains mo tifs suggestive of a transcription regulator, To date, nine APS-1-associate d mutations have been identified in the AIRE gene, including two common mut ations R257X and 1094-1106del. In addition to these two mutations, we repor t seven novel mutations in 16 APS-1 patients from North America, We found t hat 1094-1106del and R257X were the most common mutations in this populatio n of mixed geoethnic origin, accounting for 17/32 and 4/32 alleles, respect ively, Haplotype analyses suggest that both are recurrent mutations, occurr ing on several different haplotypes with closely linked markers. All the no vel mutations appear to be rare, occur ring 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, Geno type phenotype correlations for APS-1 remain difficult, suggesting that oth er genetic or environmental factors, or both, influence the clinical presen tation and disease progression in individual APS 1 patients. Hum Mutat 13:6 9-74, 1999. (C) 1999 Wiley-Liss, Inc.