Vitamin D receptor mutations in patients with hereditary 1,25-dihydroxyvitamin D-resistant rickets
Küçük Resim Yok
Tarih
2014
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Academic Press Inc Elsevier Science
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Context: 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.
Açıklama
Anahtar Kelimeler
Vitamin D, Rickets, Hypocalcemia, Mutations, Vitamin D Receptor, HVDRR, Ligand-Binding Domain, Compound Heterozygous Mutations, D-Dependent Rickets, Deoxyribonucleic-Acid, Nonsense Mutation, Missense Mutation, Chromosomal Gene, Point Mutations, Vdr Gene, Hormone
Kaynak
Molecular Genetics And Metabolism
WoS Q Değeri
Q2
Scopus Q Değeri
Q2
Cilt
111
Sayı
1
