title: Distinct clinical phenotype and immunoreactivity in Japanese siblings with autoimmune polyglandular syndrome type 1 (APS-1) associated with compound heterozygous novel AIRE gene mutations.
abstract: We herein report on two Japanese siblings with autoimmune polyglandular syndrome type 1 (APS-1). The brother, who expressed a characteristic phenotype of APS-1, had developed severe mucocutaneous candidiasis in early infancy and thereafter developed hypoparathyroidism and Addison's disease, along with a severe deterioration of his immunologic function. In contrast, the 44-year-old sister, who showed a noncharacteristic phenotype of APS-1, developed insulin-dependent diabetes with high anti-glutamic acid decarboxylase antibody, mild nail candidiasis, and autoimmune hepatitis with intact immunoreactivity. She had three susceptible human leukocyte antigen (HLA) loci for type 1 autoimmune diabetes. The expression of T cell receptor (TCR)V beta 5.1 increased in both patients, while the brother showed a widely suppressed expression of many TCRV beta families. Both individuals possessed compound heterozygous novel autoimmune regulator (AIRE) gene mutations (L29P and IVS9-1G > C). The same AIRE gene mutations can thus be associated with characteristic and noncharacteristic phenotypes of APS-1, and HLA may possibly influence the phenotype of APS-1.
authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kogawa
authors.forename: Jun
authors.initials: J
authors.lastname: Kudoh
authors.forename: Seiho
authors.initials: S
authors.lastname: Nagafuchi
authors.forename: Shouichi
authors.initials: S
authors.lastname: Ohga
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Katsuta
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ishibashi
authors.forename: Mine
authors.initials: M
authors.lastname: Harada
authors.forename: Toshiro
authors.initials: T
authors.lastname: Hara
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Shimizu
mesh_terms: D000224:Addison Disease / Q000235:genetics / Q000276:immunology / Q000473:pathology; D000328:Adult; D002178:Candidiasis, Chronic Mucocutaneous / Q000235:genetics / Q000276:immunology / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology / Q000473:pathology; D017809:Fatal Outcome; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007564:Japan; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D009154:Mutation / Q000235:genetics / Q000276:immunology; D009679:Nuclear Family; D010375:Pedigree; D010641:Phenotype; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016133:Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics* / Q000276:immunology; D000096927:AIRE Protein
chemical_list: D014157:Transcription Factors; D000096927:AIRE Protein