Autoimmune polyendocrinopathy-candidiasis-ectodermal-dystrophy (APECED) in Sicily: confirmation that R203X is the peculiar AIRE gene mutation.
BACKGROUND
Autoimmune polyendocrinopathycandidiasis-ectodermal-dystrophy (APECED), also known as autoimmune polyendocrine syndrome type 1 (APS-1) (OMIM 240300), is a very rare disease. Accepted criteria for diagnosis require the presence of at least 2 of 3 major clinical features: chronic mucocutaneous candidiasis (CMC), chronic hypoparathyroidism (CH), and Addison's disease (AD).


OBJECTIVE
We analyzed AIRE gene mutations and genotype-phenotype correlation in APECED patients originating from Sicily and in their relatives.


METHODS
In 4 patients, clinical evaluations, genetic analysis of AIRE, and APECED-related autoantibodies were performed.


RESULTS
Two patients carried the mutation R203X in homozygosis on exon 5. One had the mutation R203X combined with R139X. The fourth had the R203X mutation in heterozygosis with R257X. Expression of the disease showed wide variability of clinical manifestations. Analysis of relatives allowed the identification of 10 heterozygotes for AIRE gene mutations. None of these subjects presented major findings of APECED. Three of the 4 patients were positive for autoantibodies to interferon-ω.


CONCLUSIONS
In Sicily, R203X is confirmed to be the typical recessive and prevalent AIRE gene mutation on exon 5. Genotype-phenotype correlation failed to reveal a relationship between detected mutations and clinical expression. Mutations in heterozygosity in AIRE gene are not associated with major findings of APECED.
Endocrine Unit, Department of Biomedical Internal and Specialist Medicine, Palermo University, Palermo, Italy.
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C
Giordano
R
R
Modica
M L
ML
Allotta
V
V
Guarnotta
S
S
Cervato
S
S
Masiero
R
R
Giordano
S
S
Garelli
C
C
Betterle
D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D016884:Polyendocrinopathies, Autoimmune / Q000175:diagnosis* / Q000235:genetics*; D012802:Sicily; D014157:Transcription Factors / Q000235:genetics*; D000096927:AIRE Protein
D014157:Transcription Factors; D000096927:AIRE Protein