부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.abb.2006.09.027 Byline: Peter J. Malloy (a), Jining Wang (a), Lihong Peng (a), Sunil Nayak (b), Jeanne M. Sisk (c), Catherine C. Thompson (c), David Feldman (a) Keywords: Vitamin D; Rickets; Alopecia; Mutation; Vitamin D receptor; Gene; Calcitriol; Hairless Abstract: Hereditary vitamin D resistant rickets (HVDRR) is caused by mutations in the vitamin D receptor (VDR). Here we describe a patient with HVDRR who also exhibited some hypotrichosis of the scalp but otherwise had normal hair and skin. A 102bp insertion/duplication was found in the VDR gene that introduced a premature stop (Y401X). The patient's fibroblasts expressed the truncated VDR, but were resistant to 1,25(OH).sub.2D.sub.3. The truncated VDR weakly bound [.sup.3H]-1,25(OH).sub.2D.sub.3 but was able to heterodimerize with RXR, bind to DNA and interact with the corepressor hairless (HR). However, the truncated VDR failed to bind coactivators and was transactivation defective. Since the patient did not have alopecia or papular lesions of the skin generally found in patients with premature stop mutations this suggests that this distally truncated VDR can still regulate the hair cycle and epidermal differentiation possibly through its interactions with RXR and HR to suppress gene transactivation. Author Affiliation: (a) Division of Endocrinology, Gerontology and Metabolism, Department of Medicine, Stanford University School of Medicine, Stanford University Medical Center, Stanford, CA 94305, USA (b) Pediatric Endocrine Associates, Greenwood Village, CO 80111, USA (c) Kennedy Krieger Institute and Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA Article History: Received 28 July 2006; Revised 27 September 2006 Article Note: (footnote) [star] Supported by NIH Grant DK42482 (to D.F.).