Positional cloning of the APECED gene

Kentaro Nagamine, Pärt Peterson, Hamish S. Scott, Jun Kudo, Shinsei Minoshima, Maarit Heino, Kai J E Krohn, Maria D. Lalioti, Primus E. Mullis, Stylianos E. Antonarakis, Kazuhiko Kawasaki, Shuichi Asakawa, Fumiaki Ito, Nobuyoshi Shimizu

Research output: Contribution to journalArticle

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Abstract

Autoimmune polyglandular syndrome type I (APS 1, also called APECED) is an autosomal-recessive disorder that maps to human chromosome 21q22.3 between markers D21S49 and D21S171 by linkage studies. We have isolated a novel gene from this region, AIRE (autoimmune regulator), which encodes a protein containing motifs suggestive of a transcription factor including two zinc- finger (PHD-finger) motifs, a proline-rich region and three LXXLL motifs. Two mutations, a C→T substitution that changes the Arg 257 (CGA) to a stop codon (TGA) and an A→G substitution that changes the Lys 83 (AAG) to a Glu codon (GAG), were found in this novel gene in Swiss and Finnish APECED patients. The Arg257stop (R257X) is the predominant mutation in Finnish APECED patients, accounting for 10/12 alleles studied. These results indicate that this gene is responsible for the pathogenesis of APECED. The identification of the gene defective in APECED should facilitate the genetic diagnosis and potential treatment of the disease and further enhance our general understanding of the mechanisms underlying autoimmune diseases.

Original languageEnglish
Pages (from-to)393-398
Number of pages6
JournalNature Genetics
Volume17
Issue number4
Publication statusPublished - 1997

Fingerprint

Autoimmune Polyendocrinopathies
Organism Cloning
Genes
Amino Acid Motifs
Mutation
Terminator Codon
Zinc Fingers
Human Chromosomes
Proline
Codon
Autoimmune Diseases
Fingers
Transcription Factors
Alleles

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Nagamine, K., Peterson, P., Scott, H. S., Kudo, J., Minoshima, S., Heino, M., ... Shimizu, N. (1997). Positional cloning of the APECED gene. Nature Genetics, 17(4), 393-398.

Positional cloning of the APECED gene. / Nagamine, Kentaro; Peterson, Pärt; Scott, Hamish S.; Kudo, Jun; Minoshima, Shinsei; Heino, Maarit; Krohn, Kai J E; Lalioti, Maria D.; Mullis, Primus E.; Antonarakis, Stylianos E.; Kawasaki, Kazuhiko; Asakawa, Shuichi; Ito, Fumiaki; Shimizu, Nobuyoshi.

In: Nature Genetics, Vol. 17, No. 4, 1997, p. 393-398.

Research output: Contribution to journalArticle

Nagamine, K, Peterson, P, Scott, HS, Kudo, J, Minoshima, S, Heino, M, Krohn, KJE, Lalioti, MD, Mullis, PE, Antonarakis, SE, Kawasaki, K, Asakawa, S, Ito, F & Shimizu, N 1997, 'Positional cloning of the APECED gene', Nature Genetics, vol. 17, no. 4, pp. 393-398.
Nagamine K, Peterson P, Scott HS, Kudo J, Minoshima S, Heino M et al. Positional cloning of the APECED gene. Nature Genetics. 1997;17(4):393-398.
Nagamine, Kentaro ; Peterson, Pärt ; Scott, Hamish S. ; Kudo, Jun ; Minoshima, Shinsei ; Heino, Maarit ; Krohn, Kai J E ; Lalioti, Maria D. ; Mullis, Primus E. ; Antonarakis, Stylianos E. ; Kawasaki, Kazuhiko ; Asakawa, Shuichi ; Ito, Fumiaki ; Shimizu, Nobuyoshi. / Positional cloning of the APECED gene. In: Nature Genetics. 1997 ; Vol. 17, No. 4. pp. 393-398.
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