Abstract
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)2D). Mutations were re-created in the WT VDR cDNA and examined for 1,25(OH)2D3-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 acid change D144N; a missense mutation in exon 7 causing the amino acid change N276Y; and a 2. bp deletion in exon 3 5'-splice site (IVS3+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.
Original language | English |
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Pages (from-to) | 33-40 |
Number of pages | 8 |
Journal | Molecular Genetics and Metabolism |
Volume | 111 |
Issue number | 1 |
DOIs | |
State | Published - 2014 |
Keywords
- HVDRR
- Hypocalcemia
- Mutations
- Rickets
- Vitamin D
- Vitamin D receptor