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AIRE variations in Addison's disease and autoimmune polyendocrine syndromes (APS): partial gene deletions contribute to APS I

Genes & Immunity volume 9, pages 130–136 (2008)Cite this article

Abstract

Autoimmune Addison's disease (AAD) is often associated with other components in autoimmune polyendocrine syndromes (APS). Whereas APS I is caused by mutations in the AIRE gene, the susceptibility genes for AAD and APS II are unclear. In the present study, we investigated whether polymorphisms or copy number variations in the AIRE gene were associated with AAD and APS II. First, nine SNPs in the AIRE gene were analyzed in 311 patients with AAD and APS II and 521 healthy controls, identifying no associated risk. Second, in a subgroup of 25 of these patients, AIRE sequencing revealed three novel polymorphisms. Finally, the AIRE copy number was determined by duplex quantitative PCR in 14 patients with APS I, 161 patients with AAD and APS II and in 39 healthy subjects. In two Scandinavian APS I patients previously reported to be homozygous for common AIRE mutations, we identified large deletions of the AIRE gene covering at least exon 2 to exon 8. We conclude that polymorphisms in the AIRE gene are not associated with AAD and APS II. We further suggest that DNA analysis of the parents of patients found to be homozygous for mutations in AIRE, always should be performed.

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Acknowledgements

The following physicians have kindly provided clinical data: A-G Myhre, K Fougner, K Lima, S Skare, S Uhlving, U Schafroth and D Veimo. Dag E Undlien is thanked for giving us control DNA. The technical help from Sigrid Erdal and Elin Theodorsen is greatly acknowledged. The study has been supported by grants from Helse-Bergen, the Norwegian Research Council and the EU 6th framework programme (EurAPS).

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Author notes

  1. A S Bøe Wolff and B Oftedal: These authors contributed equally to this work.

Authors and Affiliations

  1. Institute of Medicine, University of Bergen, Bergen, Norway

    A S Bøe Wolff, B Oftedal, K Løvås & E S Husebye

  2. Department of Medicine, Haukeland University Hospital, Bergen, Norway

    A S Bøe Wolff, B Oftedal, K Løvås & E S Husebye

  3. Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway

    A S Bøe Wolff, S Johansson, O Bruland & P M Knappskog

  4. Department of Clinical Medicine, University of Bergen, Bergen, Norway

    S Johansson & P M Knappskog

  5. Biotherapeutics Group, The National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Herts, UK

    A Meager

  6. Department of Pediatrics, Kolding Hospital, Kolding, Denmark

    C Pedersen

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  1. A S Bøe Wolff
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Correspondence to A S Bøe Wolff.

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Bøe Wolff, A., Oftedal, B., Johansson, S. et al. AIRE variations in Addison's disease and autoimmune polyendocrine syndromes (APS): partial gene deletions contribute to APS I. Genes Immun 9, 130–136 (2008). https://doi.org/10.1038/sj.gene.6364457

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