Autoimmune polyendocrine syndrome type 1 (APS I) in Norway - phenotypic variation, autoantibodies and novel mutations in the autoimmune regulator (AIRE) gene. [J Clin Endocrinol Metab] Journal article | | Title | Autoimmune polyendocrine syndrome type 1 (APS I) in Norway - phenotypic variation, autoantibodies and novel mutations in the autoimmune regulator (AIRE) gene. | | Author(s) | Wolff AS, Erichsen MM, Meager A, Magitta NF, Myhre AG, Bollerslev J, Fougner KJ, Lima K, Knappskog PM, Husebye ES | | Institution | Institutes of Medicine (A.S.B.W; E.S.H.) and Clinical Medicine (N.F.M.; P.M.K.), University of Bergen, N-5021 Bergen, Norway; Department of Medicine (M.M.E.; E.S.H.) and Center of Medical Genetics and Molecular Medicine (A.S.B.W; N.F.M, P.M.K.), Haukeland University Hospital, N-5021 Bergen, Norway; Biotherapeutics (A.M.), The National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Herts, EN6 3QG, UK, Department of Pediatrics (A.G.M.) and Medicine (J.B.), Rikshospitalet-Radiumhospitalet University Hospital, N-0027 Oslo, Norway, Department of Endocrinology (K.J.F.), St. Olavs Hospital, N-7006, Trondheim, Norway; Section of Endocrinology (K.L.), Faculty Division Akershus University Hospital, University of Oslo, and Section of Endocrinology (K.L), Akershus University Hospital, 1474 Nordbyhagen, Norway. | | Source | J Clin Endocrinol Metab 2006 Nov 21. | | Abstract | Context: The autoimmune polyendocrine syndrome type I (APS I) is a rare disease which previously was difficult to diagnose. Autoantibody screening as well as mutational analysis of the "disease gene" autoimmune regulator (AIRE) are important diagnostic tools for this life threatening syndrome.
Objective: To identify all patients with APS I in Norway and correlate their clinical features with their autoantibody profiles and mutations in the autoimmune regulator (AIRE) gene.
Patients: We identified 36 Norwegian patients from 24 families with APS I (20 males, 16 females) during a nation-wide survey for patients with Addison's disease and polyendocrine syndromes, 7 of them only after their death. Research design and methods: Clinical data were collected from questionnaires and patient records. AIRE mutations were determined by DNA sequencing. Most autoantibodies were measured in RIAs against recombinant autoantigens, but anti-type I interferon (IFN) antibodies were titrated in ELISA or antiviral interferon neutralization assays.
Results: The prevalence of APS I in Norway was estimated to be about 1:90,000. Several patients exhibited a milder phenotype with few APS I disease components and onset only in late adolescent or adulthood. The others showed about the same distribution of disease components as reported in Finnish patients. Eleven different mutations were identified in the AIRE gene, six of these were novel, i.e. c.22C>T (p.Arg8Cys), c.290T>C (p.Leu97Pro), c.402delC (p.Ser135GlnfsX12), c.879 + 1G>A (p.IVS7 + 1G>A), c.1249dupC (p.Leu417ProfsX7) and c.1336T>G (p.Cys446Gly). The 13 bp deletion in exon 8 (c.967-979del13) was the most prevalent mutation, present in 23/48 (48%) of the alleles. The presence of neutralizing autoantibodies against IFN-omega was the most specific marker of APS I, being found in all but one Norwegian patient. Some other common APS I-associated autoantibodies appeared de novo during long-term follow-up of younger patients.
Conclusions: Norwegian patients with APS I clinically resemble those from Finland and other European countries, but some have milder phenotypes. In total, six new mutations were identified in the Norwegian APS I patients. Anti-type I IFN autoantibodies are easily detectable; their APS I-specificity and persistently high titers render them reliable markers of APS I, even in prodromal or atypical cases. Both the clinical features and the AIRE mutations are more diverse in the Norwegian population than previously thought. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 17118990 |
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