Autoimmune polyglandular syndrome type 1 in Russian patients: clinical variants and autoimmune regulator mutations.
BACKGROUND
Autoimmune polyglandular syndrome type 1 (APS-1) (OMIM 240300) is a rare autosomal recessive disorder associated with three major manifestations: chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency. There are, however, multiple minor components of APS-1 that induce significant phenotype variability. Subsequently, the diagnosis of APS-1 during early stages is often challenging.


OBJECTIVE
We aimed to provide clinical and mutational data for a large number of APS-1 patients in the Russian population.


METHODS
We analyzed clinical variations and component prevalence in APS-1 patients. DNA screening for autoimmune regulator (AIRE) gene mutations was performed in established APS-1 patients and in patients with the single components of chronic mucocutaneous candidiasis, hypoparathyroidism, adrenal insufficiency, or alopecia.


RESULTS
We identified 46 patients from 42 families with APS-1. Eighteen different components were present in the patients, including very rare conditions - bone dysplasia and retinitis pigmentosa. We identified 10 different mutations, 3 of which were novel (M1T, E298K, c1053_1060del). The common Finnish mutation, R257X, was the most frequent in our population, present in 64/92 (70%) of the alleles.


CONCLUSIONS
We found that the R257X AIRE mutation is common in Russian APS-1 patients. The majority of children with hypoparathyroidism and chronic mucocutaneous candidiasis were carriers of the AIRE mutations.
Orlova
Elizaveta M
EM
Endocrinology Research Centre, Institute of Paediatric Endocrinology, Moscow, Russia. elizaveta.orlova @ mail.ru
Bukina
Anna M
AM
Kuznetsova
Elvira S
ES
Kareva
Maria A
MA
Zakharova
Ekaterina U
EU
Peterkova
Valentina A
VA
Dedov
Ivan I
II
D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D016884:Polyendocrinopathies, Autoimmune / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology*; D012426:Russia
D001323:Autoantibodies