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

Maria Cristina Rosatelli, Alessandra Meloni, Antonella Meloni, Marcella Devoto, Antonio Cao, Hamish S. Scott, Part Peterson, Maarit Heino, Kai J.E. Krohn, Kentaro Nagamine, Jun Kudoh, Nobuyoshi Shimizu, Stylianos E. Antonarakis

Research output: Contribution to journalArticlepeer-review

227 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)428-434
Number of pages7
JournalHuman genetics
Issue number4
Publication statusPublished - 1998
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'A common mutation in Sardinian autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients'. Together they form a unique fingerprint.

Cite this