{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T01:02:50Z","timestamp":1785805370938,"version":"3.56.0"},"reference-count":23,"publisher":"The Endocrine Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We report the association of an undescribed, reversible metaphyseal dysplasia (RMD) with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in two patients, one homozygous and one heterozygous for a 13-bp deletion in exon 8 of the autoimmune regulator (AIRE) gene. One patient also had a novel deletion in exon 6, resulting in a frameshift mutation and introduction of a STOP codon in exon 10. Their APECED phenotypes differed, but both patients developed progressive skeletal deformities and growth failure from early childhood. Radiological examination suggested a generalized abnormality of endochondral ossification, with irregular, flared, radioopaque regions in the metaphyses, subjacent to the growth plates. Histopathology in patient 1 showed islands of calcified cartilage within bone, consistent with impaired coupling of cartilage resorption with vascular invasion and ossification. Despite discordance for puberty, both patients experienced radiological resolution of their bone disease in their mid-teens, with improvement in histopathology in patient 1. RMD may constitute a rare phenotypic variation of APECED, possibly resulting from autoimmunity directed against skeletal proteins. We also demonstrated AIRE expression in chondrocytes derived from human fetal growth plates, primary culture of human chondrocytes, and two chondrosarcoma cell lines, suggesting a potential role for abnormal AIRE expression in the development of RMD.<\/jats:p>","DOI":"10.1210\/jc.2003-030089","type":"journal-article","created":{"date-parts":[[2003,10,13]],"date-time":"2003-10-13T17:42:51Z","timestamp":1066066971000},"page":"4576-4585","source":"Crossref","is-referenced-by-count":15,"title":["Reversible Metaphyseal Dysplasia, a Novel Bone Phenotype, in Two Unrelated Children with Autoimmunepolyendocrinopathy-Candidiasis-Ectodermal Dystrophy: Clinical and Molecular Studies"],"prefix":"10.1210","volume":"88","author":[{"given":"Mark","family":"Harris","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Sydney Children\u2019s Hospital (M.H., J.W.), Randwick, New South Wales 2031, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ouafae","family":"Kecha","sequence":"additional","affiliation":[{"name":"Endocrine Service, Department of Pediatrics, Ho\u0302pital Ste-Justine, Universite\u0301 de Montre\u0301al (O.K., C.D., J.S.-R.), Montre\u0301al, Que\u0301bec, H3T 1E2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheri","family":"Deal","sequence":"additional","affiliation":[{"name":"Endocrine Service, Department of Pediatrics, Ho\u0302pital Ste-Justine, Universite\u0301 de Montre\u0301al (O.K., C.D., J.S.-R.), Montre\u0301al, Que\u0301bec, H3T 1E2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Rolfe","family":"Howlett","sequence":"additional","affiliation":[{"name":"School of Pathology, University of New South Wales (C.R.H.), Randwick, New South Wales 2031, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothee","family":"Deiss","sequence":"additional","affiliation":[{"name":"Charite\u0301, Humbold University (D.D.), Berlin, D-13353, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivienne","family":"Tobias","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology, South Eastern Area Laboratory Services at Sydney Children\u2019s Hospital (V.T.), Randwick, New South Wales 2031, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Simoneau-Roy","sequence":"additional","affiliation":[{"name":"Endocrine Service, Department of Pediatrics, Ho\u0302pital Ste-Justine, Universite\u0301 de Montre\u0301al (O.K., C.D., J.S.-R.), Montre\u0301al, Que\u0301bec, H3T 1E2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Walker","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Sydney Children\u2019s Hospital (M.H., J.W.), Randwick, New South Wales 2031, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071616445579900_R1","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/S0889-8529(01)00013-5","article-title":"APS-I\/APECED: the clinical disease and therapy.","volume":"31","author":"Perheentupa","year":"2002","journal-title":"Endocrinol Metab Clin North Am"},{"key":"2020071616445579900_R2","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/S0889-8529(01)00011-1","article-title":"Population genetics and functions of the autoimmune regulator (AIRE).","volume":"31","author":"Kumar","year":"2002","journal-title":"Endocrinol Metab Clin North Am"},{"key":"2020071616445579900_R3","doi-asserted-by":"crossref","first-page":"16802","DOI":"10.1074\/jbc.M908944199","article-title":"The autoimmune regulator protein has transcriptional transactivating properties and interacts with the common coactivator CREB-binding protein.","volume":"275","author":"Pitkanen","year":"2000","journal-title":"J Biol Chem"},{"key":"2020071616445579900_R4","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1093\/hmg\/8.2.277","article-title":"AIRE encodes a nuclear protein co-localizing with cytoskeletal filaments: altered sub-cellular distribution of mutants lacking the PHD zinc fingers.","volume":"8","author":"Rinderle","year":"1999","journal-title":"Hum Mol Genet"},{"key":"2020071616445579900_R5","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1086\/302765","article-title":"Mutations in the AIRE gene: effects on subcellular location and transactivation function of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy protein.","volume":"66","author":"Bjorses","year":"2000","journal-title":"Am J Hum Genet"},{"key":"2020071616445579900_R6","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1177\/002215540104900207","article-title":"Subcellular location and expression pattern of autoimmune regulator (Aire), the mouse orthologue for human gene defective in autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED).","volume":"49","author":"Halonen","year":"2001","journal-title":"J Histochem Cytochem"},{"key":"2020071616445579900_R7","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1093\/nar\/19.2.408","article-title":"A rapid procedure for extracting genomic DNA from leukocytes.","volume":"19","author":"John","year":"1991","journal-title":"Nucleic Acids Res"},{"key":"2020071616445579900_R8","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/ng1297-399","article-title":"An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. 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