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Molecular background of polyendocrinopathy–candidiasis–ectodermal dystrophy syndrome in a Polish population: novel AIRE mutations and an estimate of disease prevalence
Author(s) -
Stolarski B,
Pronicka E,
Korniszewski L,
Pollak A,
Kostrzewa G,
Rowińska E,
Włodarski P,
Skórka A,
Gremida M,
Krajewski P,
Ploski R
Publication year - 2006
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.2006.00690.x
Subject(s) - hypoparathyroidism , missense mutation , autoimmune regulator , medicine , genetics , mutation , population , chronic mucocutaneous candidiasis , genotype , fabry disease , disease , autoimmune disease , biology , gastroenterology , gene , environmental health
Autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED) is an autosomal‐recessive autoimmune disease caused by autoimmune regulator gene mutations. The aim of this study was to examine the mutation profile of Polish APECED patients, determine the carrier rate of the most frequent mutation(s) and estimate disease prevalence. While studying 14 unrelated patients, we identified three novel mutations (c.1A>T, affecting the start codon; [IVS1 + 1G>C; IVS1 + 5delG], a complex mutation affecting splice site; c. 908G>C, p.R303P, a missense mutation in plant homeodomain (PHD) and three previously reported mutations (c.769C>T, p.R257X; c.967_979del13bp, C322fsX372; c.931delT, p.C311fsX376). Eleven patients had mutations on both chromosomes, whereas in three patients only a single alteration with proven or likely pathogenic effect was detected. The most frequent was the p.R257X mutation (71% of chromosomes); its carriage rate was assessed in the background population. Analysis of 2008 samples showed eight heterozygotes, indicating the frequency of 0.40% (1:250) and the disease prevalence – 1:129,000 (95% confidence interval: 1:555,000 to 1:30,000). Comparison with an epidemiological estimate (1:619,000, derived for women) suggested that in Poland, APECED is underdiagnosed. Among the patients, no genotype/phenotype correlations were found, but we noted that women had earlier onset of hypoparathyroidism ( p < 0.02) and were younger at diagnosis ( p < 0.05) than men.