Document Detail

A novel mutation of the autoimmune regulator gene in an Italian kindred with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, acting in a dominant fashion and strongly cosegregating with hypothyroid autoimmune thyroiditis.
MedLine Citation:
PMID:  11600535     Owner:  NLM     Status:  MEDLINE    
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy is a rare autosomal recessive disorder characterized by hypoparathyroidism, adrenal failure, chronic mucocutaneous candidiasis, and ectodermal dystrophies and other organ-specific autoimmune diseases. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy is caused by mutations of the autoimmune regulator gene. We identified an Italian family with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy and a pattern of inheritance suggestive of a dominant mechanism. Serological and clinical studies showed a high prevalence of hypothyroid autoimmune thyroiditis in affected members with classical autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Direct sequencing of the entire coding region of the autoimmune regulator gene revealed the presence in the proband of a novel missense (G228W) mutation in exon 6 in a heterozygous state. The same heterozygous mutation was identified in all family members with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy and/or hypothyroid autoimmune thyroiditis. None of the unaffected family members and 50 unrelated Italian controls carried the mutation. In contrast with all other autoimmune regulator mutations reported in families, the novel G228W mutation acts in a dominant fashion in our family, as only one heterozygous mutation was found in the entire coding sequence of the autoimmune regulator gene in the proband. Moreover, analysis of the family tree showed direct transmission of the hypothyroid autoimmune thyroiditis/polyendocrinopathy-candidiasis-ectodermal dystrophy phenotype to the offspring in each generation in the absence of consanguinity, further supporting a dominant inheritance. The G228W closely cosegregated with hypothyroid autoimmune thyroiditis in our family, whereas a low penetrance of the full autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy phenotype was observed. In conclusion, we report a novel mutation of the autoimmune regulator gene in a family with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, closely cosegregating with hypothyroid autoimmune thyroiditis. The G228W mutation acts in a dominant fashion and may shed light on the structure-function relationship of the autoimmune regulator protein.
F Cetani; G Barbesino; S Borsari; E Pardi; L Cianferotti; A Pinchera; C Marcocci
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  86     ISSN:  0021-972X     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2001 Oct 
Date Detail:
Created Date:  2001-10-15     Completed Date:  2001-11-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4747-52     Citation Subset:  AIM; IM    
Dipartimento di Endocrinologia e Metabolismo, Universita' degli Studi di Pisa, Via Paradisa 2, 56124 Pisa, Italy.
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MeSH Terms
Aged, 80 and over
Genes, Regulator*
Linkage (Genetics)
Middle Aged
Parathyroid Hormone / blood
Polyendocrinopathies, Autoimmune / genetics*,  immunology,  metabolism
Thyroiditis, Autoimmune / genetics*
Thyrotropin / blood
Transcription Factors / genetics*
Reg. No./Substance:
0/APECED protein; 0/Parathyroid Hormone; 0/Transcription Factors; 9002-71-5/Thyrotropin

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