Malloy, Peter J.Tasic, VeliborTaha, DorisTutunculer, FilizYing, Goh SiokYin, Loke KahWang, Jining2024-06-122024-06-1220141096-71921096-7206https://doi.org/10.1016/j.ymgme.2013.10.014https://hdl.handle.net/20.500.14551/24591Context: Hereditary vitamin D resistant rickets (HVDRR), also known as vitamin D-dependent rickets type II, is an autosomal recessive disorder characterized by the early onset of rickets with hypocalcemia, secondary hyperparathyroidism and hypophosphatemia and is caused by mutations in the vitamin D receptor (VDR) gene. The human gene encoding the VDR is located on chromosome 12 and comprises eight coding exons and seven introns. Objectives, patients, and methods: We analyzed the VDR gene of 5 previously unreported patients, two from Singapore and one each from Macedonia (former Yugoslav Republic), Saudi Arabia and Turkey. Each patient had clinical and radiographic features of rickets, hypocalcemia, and the 4 cases that had the measurement showed elevated serum concentrations of 1,25-dihydroxyvitamin D (1,25(OH)(2)D). Mutations were re-created in the WT VDR cDNA and examined for 1,25(OH)(2)D-3-mediated transactivation in COS-7 monkey kidney cells. Results: Direct sequencing identified four novel mutations and two previously described mutations in the VDR gene. The novel mutations included a missense mutation in exon 3 causing the amino acid change C60W; a missense mutation in exon 4 causing the amino add change D144N; a missense mutation in exon 7 causing the amino add change N276Y; and a 2 bp deletion in exon 3 5'-splice site (IVS3 Delta + 4-5) leading to a premature stop. Conclusions: These 4 unique mutations add to the previous 45 mutations identified in the VDR gene in patients with HVDRR. (C) 2013 Elsevier Inc. All rights reserved.en10.1016/j.ymgme.2013.10.014info:eu-repo/semantics/openAccessVitamin DRicketsHypocalcemiaMutationsVitamin D ReceptorHVDRRLigand-Binding DomainCompound Heterozygous MutationsD-Dependent RicketsDeoxyribonucleic-AcidNonsense MutationMissense MutationChromosomal GenePoint MutationsVdr GeneHormoneArticle11113340Q2WOS:0003301581000052-s2.0-8489182793224246681Q2