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Human Genetics

, Volume 103, Issue 4, pp 428–434 | Cite as

A common mutation in Sardinian autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients

  • M. C. Rosatelli
  • Alessandra Meloni
  • Antonella Meloni
  • Marcella Devoto
  • Antonio Cao
  • H. S. Scott
  • Pärt Peterson
  • Maarit Heino
  • Kai J. E. Krohn
  • Kentaro Nagamine
  • J. Kudoh
  • Nobuyoshi Shimizu
  • Stylianos E. Antonarakis
  • Group 1: Maria Cristina Rosatelli · Alessandra Meloni Antonella Meloni · Marcella Devoto · Antonio Cao Group 2: Hamish S. Scott · Pärt Peterson Maarit Heino · Kai J. E. Krohn · Kentaro Nagamine Jun Kudoh · Nobuyoshi Shimizu Stylianos E. Antonarakis
Original investigation

Abstract

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED; also called APS-1,) is a rare autosomal recessive disorder that is more frequent in certain isolated populations. It is characterized by two of the three major clinical symptoms that may be present: Addison’s disease, and/or hypoparathyroidism and/or chronic mucocutaneous candidiasis. We have recently identified the gene for APECED, which we termed AIRE (for autoimmune regulator). AIRE is expressed in thymus, lymph nodes and fetal liver, and encodes a protein with two putative zinc fingers and other motifs suggestive of a transcriptional regulator. Seven mutations have been described to date, including R257X, the predominant Finnish and northern Italian APECED allele, which has also been observed in other patients of diverse origin on different haplotypes. A 13-bp deletion (1094–1106del) has also been observed in several patients of different geo-ethnic origin. The other described mutations appear to be rare. We present mutational analyses of the AIRE gene in ten Sardinian APECED families and show that there is a mutation, R139X, associated with one predominant haplotype unique to the Sardinian patients (18/20 independent alleles). The carrier frequency of R139X in Sardinia is 1.7%, giving an estimated population frequency of APECED of 1/14,400. Using linkage disequilibrium data, the estimated age of the R139X mutation is between 20 and 25 generations. A previously described 13-bp deletion was also observed on an allele of one patient. The identification of a single common Sardinian APECED mutation will facilitate its genetic diagnosis. Given the carrier frequency of R139X in the Sardinian population, AIRE may be implicated in the pathogenesis of other autoimmune diseases in the Sardinian population, particularly those affecting the endocrine system.

Keywords

Candidiasis Carrier Frequency Hypoparathyroidism Autosomal Recessive Disorder Rare Autosomal Recessive Disorder 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • M. C. Rosatelli
    • 1
  • Alessandra Meloni
    • 1
  • Antonella Meloni
    • 2
  • Marcella Devoto
    • 3
  • Antonio Cao
    • 1
  • H. S. Scott
    • 4
  • Pärt Peterson
    • 5
  • Maarit Heino
    • 5
  • Kai J. E. Krohn
    • 5
  • Kentaro Nagamine
    • 6
  • J. Kudoh
    • 6
  • Nobuyoshi Shimizu
    • 6
  • Stylianos E. Antonarakis
    • 4
  • Group 1: Maria Cristina Rosatelli · Alessandra Meloni Antonella Meloni · Marcella Devoto · Antonio Cao Group 2: Hamish S. Scott · Pärt Peterson Maarit Heino · Kai J. E. Krohn · Kentaro Nagamine Jun Kudoh · Nobuyoshi Shimizu Stylianos E. Antonarakis
  1. 1.Istituto di Clinica e Biologia dell’Età evolutiva, Università degli Studi di Cagliari, I-09121, Cagliari, Italy Tel.: +39-70-6095653, Fax: +39-70-503696, e-mail: crosatel@mcweb.unica.itIT
  2. 2.Istituto di Ricerca sulle Talassemie ed Anemie Mediterranee, CNR, Cagliari, ItalyIT
  3. 3.Laboratory of Statistical Genetics, Rockefeller University, New York, N.Y., USAUS
  4. 4.Laboratory of Human Molecular Genetics, Department of Genetics and Microbiology, University of Geneva Medical School, 1 rue Michel Servet, CH-1211 Geneva 4, Switzerland e-mail: Hamish.Scott@medecine.unige.ch, Tel.: +41-22-702-5719, Fax: +41-22-702-5706CH
  5. 5.Institute of Medical Technology and University Hospital, University of Tampere, FIN-33101 Tampere, FinlandFI
  6. 6.Department of Molecular Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanJP

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