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Detection of a complete AIRE gene deletion and two additional novel mutations in a cohort of patients with atypical phenotypic variants of APS-1

K Trebusak Podkrajsek, University Children's Hospital, Centre for Medical Genetics, University Medical Centre Ljubljana, Ljubljana, Slovenia
T Milenkovic, Mother and Child Health Care Institute of Serbia, Belgrade, Serbia And Montenegro
R Odink, Department of Pediatrics, Catharina Ziekenhuis, Eindhoven, Netherlands
H Claahsen, Department of Metabolic and Endocrine Disease, University Medical Center St. Radboud, Nijmegen, Netherlands
N Bratanic, University Children's Hospital, Department of Pediatric Endocrinology, Diabetes and Metabolism, University Medical Centre Ljubljana, Ljubljana, Slovenia
T Hovnik, University Children's Hospital, Centre for Medical Genetics, University Medical Centre Ljubljana, Ljubljana, Slovenia
T Battelino, University Children's Hospital, Department of Pediatric Endocrinology, Diabetes and Metabolism, University Medical Centre Ljubljana, Ljubljana, Slovenia

Correspondence: Katarina Trebusak Podkrajsek, Email: katarina.trebusak{at}kclj.si

Abstract

Objective: Autoimmune polyglandular syndrome type 1 (APS-1) is characterised by multiple autoimmune diseases. Detection of AIRE (autoimmune regulator) 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, 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.

Conclusions: AIRE mutation detection was valuable in diagnostics of APS-1 in patients with atypical presentation. Chronic otitis media possibly broadened the cluster of APS-1 manifestations.