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

Luciana Cosentino de Macedo, Fernanda Caroline Soardi, Nayla Ananias, Vera Maria Santoro Belangero, Sumara Zuazani Pinto Rigatto, Maricilda Palandi De-Mello, Lília D'Souza-Li
2008 Arquivos brasileiros de endocrinologia e metabologia  
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
more » ... n 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.
doi:10.1590/s0004-27302008000800007 pmid:19169476 fatcat:d3e6fg6hr5h7ni2gywz7sjvqju