{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T19:56:26Z","timestamp":1791143786150,"version":"4.1.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2006,6,1]],"date-time":"2006-06-01T00:00:00Z","timestamp":1149120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We report here the first association between vitamin D\u2013resistant rickets, alopecia, and type 1 diabetes in a child with compound heterozygous mutations in the VDR gene. Transfection studies suggest dissociated effects of VDR gene mutations on the regulation of genes involved in vitamin D metabolism and dendritic cell maturation.<\/jats:p>\n               <jats:p>Introduction: Whereas vitamin D may play a role in the immune tolerance process, no patient has been reported to associate hereditary vitamin D\u2013resistant rickets (HVDRR) and an autoimmune disease, and no attempt has been made to delineate the outcome of mutations of the vitamin D receptor (VDR) on the transcription of genes controlling immune tolerance.<\/jats:p>\n               <jats:p>Materials and Methods: The VDR gene was analyzed in a child with vitamin D\u2013resistant rickets, total alopecia, and early childhood\u2013onset type 1 diabetes. Patient's fibroblasts and COS-7 cells transfected with wildtype or mutant VDRs were studied for ligand-binding capacity, transactivation activity using two gene promoters [CYP-24, a classical 1,25(OH)2D3-responsive gene, and relB, a critical NF-\u03baB component for regulation of dendritic cell differentiation], VDR-RXR heterodimers association to CYP 24 VDREs by gel mobility shift assays, and co-activator binding by Glutathione-S-transferase pull-down assays.<\/jats:p>\n               <jats:p>Results: Two novel compound heterozygous mutations (L263R and R391S) were identified in the VDR ligand-binding domain in this child. Both mutations significantly impaired VDR ligand-binding capacity but had dissociated effects on CYP-24 and RelB promoter responses to vitamin D. CYP 24 response binding to SRC-1 and RXR-heterodimer binding to CYP24 VDREs were abolished in L263R mutants but normal or partially altered in R391S mutants. In the opposite, RelB responses to vitamin D were close to normal in L263R mutants but abolished in R391S mutants.<\/jats:p>\n               <jats:p>Conclusions: We report the first clinical association between HVDRR, total alopecia, and early childhood\u2013onset type 1 diabetes. Mutations in the VDR ligand-binding domain may hamper the 1,25(OH)2D3\u2013mediated relB responses, an effect that depends on the site of the VDR mutation and cannot be anticipated from VDR ligand-binding ability or CYP-24 response. Based on these results, we propose to survey the immune function in patients with HVDRR, including those with moderate features of rickets.<\/jats:p>","DOI":"10.1359\/jbmr.060307","type":"journal-article","created":{"date-parts":[[2006,6,5]],"date-time":"2006-06-05T15:34:04Z","timestamp":1149521644000},"page":"886-894","source":"Crossref","is-referenced-by-count":51,"title":["Vitamin D\u2013Resistant Rickets and Type 1 Diabetes in a Child With Compound Heterozygous Mutations of the Vitamin D Receptor (L263R and R391S): Dissociated Responses of the CYP-24 and <i>rel-B<\/i> Promoters to 1,25-Dihydroxyvitamin D3"],"prefix":"10.1093","volume":"21","author":[{"given":"Minh","family":"Nguyen","sequence":"first","affiliation":[{"name":"INSERM Unit\u00e9 561, H\u00f4pital St Vincent de Paul, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnold","family":"d'Alesio","sequence":"additional","affiliation":[{"name":"INSERM Unit\u00e9 561, H\u00f4pital St Vincent de Paul, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Marc","family":"Pascussi","sequence":"additional","affiliation":[{"name":"INSERM Unit\u00e9 632, Universit\u00e9 Montpellier I, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew D","family":"Griffin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyang","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, 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