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Lookup NU author(s): Professor Simon PearceORCiD, Professor Timothy Cheetham, Dr Helen Imrie, Dr Bijayeswar Vaidya, Professor Rudy Bilous, Denise Carr, Glynis Williams, Professor Pat Kendall-Taylor
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Autoimmune polyendocrinopathy type 1 (APS1) is an autosomal recessive disorder characterized by autoimmune hypoparathyroidism, autoimmune adrenocortical failure, and mucocutaneous candidiasis. Recently, an autoimmune regulator gene (AIRE-1), which is located on chromosome 21q22.3, has been identified, and mutations in European kindreds with APS1 have been described. We used SSCP analysis and direct DNA sequencing to screen the entire 1,635-bp coding region of AIRE-1 in 12 British families with APS1. A 13-bp deletion (964del13) was found to account for 17 of the 24 possible mutant AIRE-1 alleles, in our kindreds. This mutation was found to occur de novo in one affected subject. A common haplotype spanning the AIRE-1 locus was found in chromosomes that carried the 964del13 mutation, suggesting a founder effect in our population. One of 576 normal subjects was also a heterozygous carrier of the 964del13 mutation. Six other point mutations were found in AIRE-1, including two 1-bp deletions, three missense mutations (R15L, L28P, and Y90C), and a nonsense mutation (R257*). The high frequency of the 964del13 allele and the clustering of the other AIRE-1 mutations may allow rapid molecular screening for APS1 in British kindreds. Furthermore, the prevalence of the 964del13 AIRE-1 mutation may have implications in the pathogenesis of the more common autoimmune endocrinopathies in our population.
Author(s): Pearce SHS, Cheetham TD, Imrie H, Vaidya BJ, Barnes ND, Bilous RW, Carr D, Meeran K, Shaw NJ, Smith CS, Toft AD, Williams G, Kendall-Taylor P
Publication type: Article
Publication status: Published
Journal: American Journal of Human Genetics
Year: 1998
Volume: 63
Issue: 6
Pages: 1675-1684
Print publication date: 01/12/1998
ISSN (print): 0002-9297
ISSN (electronic): 1537-6605
Publisher: Cell Press
URL: http://dx.doi.org/10.1086/302145
DOI: 10.1086/302145
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