title: A unique insertion/duplication in the VDR gene that truncates the VDR causing hereditary 1,25-dihydroxyvitamin D-resistant rickets without alopecia.
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 102 bp 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)2D3. The truncated VDR weakly bound [3H]-1,25(OH)2D3 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.
authors.affiliation: Division of Endocrinology, Gerontology and Metabolism, Department of Medicine, Stanford University School of Medicine, Stanford University Medical Center, Stanford, CA 94305, USA. malloy@cmgm.stanford.edu
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Malloy
authors.forename: Jining
authors.initials: J
authors.lastname: Wang
authors.forename: Lihong
authors.initials: L
authors.lastname: Peng
authors.forename: Sunil
authors.initials: S
authors.lastname: Nayak
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Sisk
authors.forename: Catherine C
authors.initials: CC
authors.lastname: Thompson
authors.forename: David
authors.initials: D
authors.lastname: Feldman
mesh_terms: D000505:Alopecia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002117:Calcitriol / Q000494:pharmacology; D018389:Codon, Nonsense; D053098:Familial Hypophosphatemic Rickets / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D016254:Mutagenesis, Insertional; D017354:Point Mutation; D011485:Protein Binding / Q000235:genetics; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000473:pathology; D015533:Transcriptional Activation / Q000235:genetics; D014815:Vitamins / Q000494:pharmacology
chemical_list: D018389:Codon, Nonsense; D018167:Receptors, Calcitriol; D014815:Vitamins; D002117:Calcitriol