Novel mutations of the autoimmune regulator gene in two siblings with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy

Tomohiro Ishii, Yoshimi Suzuki, Naoki Ando, Nobutake Matsuo, Tsutomu Ogata

研究成果: Article査読

50 被引用数 (Scopus)

抄録

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is the first multiple autoimmune disease that has been shown to be caused by mutations of a single gene named autoimmune regulator (AIRE). Fourteen different mutations of the AIRE gene have been identified in 61 patients from 55 families with APECED. However, there has been no report documenting AIRE gene mutations in the Asian population. We report on 2 siblings with variable manifestations of APECED who were born to a Japanese mother and a Korean father. The 11-yr-old girl had intractable thrush and ungual candidiasis, hypoparathyroidism, and occipital alopecia. The 9-yr-old boy had mild ungual candidiasis alone. Direct sequencing revealed novel frameshift mutations of the AIRE gene: an insertion of a cytosine at nucleotide 29635 at the exon 10 (29635insC), which should lead to a premature termination at the codon 371, producing a truncated protein missing the second plant homeodomain-type zinc finger motif and the third LXXLL motif, and a deletion of a guanine at nucleotide 33031 at the exon 13 (33031delG), which should result in a premature termination at the codon 520, yielding a truncated protein missing the third LXXLL motif. The mother was heterozygous for 29635insC, and the father was heterozygous for 33031delG. The frameshift mutations were undetected in 40 alleles of 20 Japanese control subjects. The results imply that the C-terminus of AIRE protein including the third LXXLL motif plays a critical role in the development of APECED, and that the phenotypic spectrum can vary between siblings with the same mutations.

本文言語English
ページ(範囲)2922-2926
ページ数5
ジャーナルJournal of Clinical Endocrinology and Metabolism
85
8
DOI
出版ステータスPublished - 2000 12 1

ASJC Scopus subject areas

  • 内分泌学、糖尿病および代謝内科学
  • 生化学
  • 内分泌学
  • 臨床生化学
  • 生化学、医学

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