Detection of a complete autoimmune regulator gene deletion and two additional novel mutations in a cohort of patients with atypical phenotypic variants of autoimmune polyglandular syndrome type 1

Objective: Autoimmune polyglandular syndrome type 1 (APS-1) is characterised by multiple autoimmune diseases. Detection of autoimmune regultory (AIRE) gene mutations facilitates timely and precise diagnosis. Design: AIRE mutation detection was performed in it cohort of II patients. Two did not meet clinical APS-I criteria and several started with atypical presentation. Methods: Sequencing and TaqMan genotyping were used to identify AIRE mutations. Complete AIRE deletion was confirmed and framed by, real-time PCR, long-range amplification and analysis of the microsatellite markers. Results: Seven different mutations were detected, three were novel: c.892G>A in exon 8. silent and a complete deletion of a single AIRE mutation c.462A>T ill exon most likely affecting splicing allele ((?_68)_(1567-14_?)del). Novel (chronic otitis) and rare (systemic juvenile rheumatoid arthritis, autoimmune bronchiolitis, epilepsy) clinical presentations were observed. Conclusions: AIRE mutation detection Was valuable in the diagnostics of APS-1 ill patients with atypical presentation. Chronic otitis media possibly broadened the cluster of APS-1 manifestations.