{"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":1791143786179,"version":"4.1.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2002,9,1]],"date-time":"2002-09-01T00:00:00Z","timestamp":1030838400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Bone &amp; Mineral Res"],"published-print":{"date-parts":[[2002,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In this study, two related young children, brother and sister, exhibited severe vitamin D\u2010resistant rickets without alopecia. Sequence analysis of the total vitamin D receptor (VDR) cDNA from skin fibroblasts revealed a substitution of the unique tryptophan of the VDR by arginine at amino acid 286 (W286R). Cultured skin fibroblasts of the two patients expressed normal\u2010size VDR protein (immunocytochemistry and Western blotting) and normal length VDR mRNA (Northern blotting). But, these fibroblasts, as well as COS\u20107 cells transfected with the W286R mutant, failed to bind 3H 1,25\u2010dihydroxyvitamin D<jats:sub>3<\/jats:sub> [1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub>]. The tryptophan substitution did not affect VDR trafficking toward the nucleus but abolished the 24\u2010hydroxylase gene response to 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub>, even at 10<jats:sup>\u22126<\/jats:sup> M concentrations. In conclusion, this case report of a new family with hereditary vitamin D\u2010 resistant rickets (HVDRR) emphasizes the crucial role of the VDR tryptophan for ligand binding and for transactivation of 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> target genes. It clearly shows the clinical significance of this VDR amino acid for calcium homeostasis and bone mineralization. This observation suggests further that the presence of a stable VDR\u2010bound ligand may not be obligatory for normal hair follicle development.<\/jats:p>","DOI":"10.1359\/jbmr.2002.17.9.1728","type":"journal-article","created":{"date-parts":[[2006,4,27]],"date-time":"2006-04-27T05:28:41Z","timestamp":1146115721000},"page":"1728-1737","source":"Crossref","is-referenced-by-count":41,"title":["Tryptophan Missense Mutation in the Ligand\u2010Binding Domain of the Vitamin D Receptor Causes Severe Resistance to 1,25\u2010Dihydroxyvitamin D"],"prefix":"10.1093","volume":"17","author":[{"given":"T. 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