Mutations in the vitamin D receptor gene in four patients with hereditary 1,25-dihydroxyvitamin D-resistant rickets

• Autor(a) principal: Macedo,Luciana Cosentino de
• Data de Publicação: 2008
• Outros Autores: Soardi,Fernanda Caroline, Ananias,Nayla, Belangero,Vera Maria Santoro, Rigatto,Sumara Zuazani Pinto, De-Mello,Maricilda Palandi, D'Souza-Li,Lília
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Arquivos Brasileiros de Endocrinologia & Metabologia (Online)
• Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0004-27302008000800007
• topic: Rickets; Bone deformities; Hypocalcemia; Vitamin D

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.