Author/Editor		Trebušak-Podkrajsek, Katarina; Milenković, Tatjana; Odink, Roelof J; Claasen-van der, Grinten; Bratanič, Nina; Hovnik, Tinka; Battelino, Tadej
Title		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
Type		članek
Source		Eur J Endocrinol
Vol. and No.		Letnik 159, št. 5
Publication year		2008
Volume		str. 633-9
Language		eng
Abstract		Objective: Autoimmune polyglandular syndrome type 1 (APS-1) is characterised by multiple autoimmune diseases. Detection of autoimmune regulator (AIRE) gene mutations facilitates timely and precise diagnosis. Design: AIRE mutation detection was performed in a cohort of 11 patients. Two did not meet clinical APS-1 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 mutation c.462A>T in exon 3 most likely affecting splicing, and a complete deletion of a single AIRE allele ((?_68)_(1567-14_?)del). Novel (chronic otitis) and rare (systemic juvenile rheumatoid arthritis, autoimmune bronchiolitis, epilepsy) clinical presentations were observed. Conclusion: AIRE mutation detection was valuable in the diagnostics of APS-1 in patients with atypical presentation. Chronic otitis media possibly broadened the cluster of APS-1 manifestations.
Descriptors		GENE DELETION GENETIC SCREENING ADULT CHILD COHORT STUDIES DNA MUTATIONAL ANALYSIS HETEROZYGOTE MICROSATELLITE REPEATS PHENOTYPE POINT MUTATION POLYENDOCRINOPATHIES, AUTOIMMUNE TRANSCRIPTION FACTORS