title: Mutations in the vitamin D receptor gene in four patients with hereditary 1,25-dihydroxyvitamin D-resistant rickets.
abstract: Mutations in the vitamin D receptor (VDR) are associated to the hereditary 1,25-dihydroxivitamin D-resistant rickets. The objectives of this work are: search for mutations in the VDR and analyze their functional consequences in four Brazilian children presented with rickets and alopecia. The coding region of the VDR was amplified by PCR e direct sequenced. We identified three mutations: two patients had the same mutation in exon 7 at aminoacid position 259 (p.Q259E); one patient had a mutation in exon 8 at codon 319 (p.G319V) and another one had a mutation in exon 3 leading to a truncated protein at position 73 (p.R73X). Functional studies of the mutant receptors of fibroblast primary culture, from patients' skin biopsy treated with increasing doses of 1,25(OH)2 vitamin D showed that VDR mutants were unable to be properly activated and presented a reduction in 24-hydroxylase expression level.
authors.affiliation: Center for Investigation in Pediatrics, Campinas, SP, Brazil.
authors.forename: Luciana Cosentino de
authors.initials: LC
authors.lastname: Macedo
authors.forename: Fernanda Caroline
authors.initials: FC
authors.lastname: Soardi
authors.forename: Nayla
authors.initials: N
authors.lastname: Ananias
authors.forename: Vera Maria Santoro
authors.initials: VM
authors.lastname: Belangero
authors.forename: Sumara Zuazani Pinto
authors.initials: SZ
authors.lastname: Rigatto
authors.forename: Maricilda Palandi
authors.initials: MP
authors.lastname: De-Mello
authors.forename: Lília
authors.initials: L
authors.lastname: D'Souza-Li
mesh_terms: D000505:Alopecia / Q000188:drug therapy / Q000235:genetics*; D001483:Base Sequence; D002117:Calcitriol / Q000627:therapeutic use; D002648:Child; D053098:Familial Hypophosphatemic Rickets / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D008297:Male; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase; D014815:Vitamins / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D014815:Vitamins; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D002117:Calcitriol