Two mutations causing vitamin D resistant rickets: modelling on the basis of steroid hormone receptor DNA‐binding domain crystal structures

@article{Rut1994TwoMC,
  title={Two mutations causing vitamin D resistant rickets: modelling on the basis of steroid hormone receptor DNA‐binding domain crystal structures},
  author={Andrew R. Rut and Y. Hewlson and Kristleifur Kristj{\'a}nsson and Ben Luisl and Mark R. Hughes and J. L. H. O'riordan},
  journal={Clinical Endocrinology},
  year={1994},
  volume={41}
}
OBJECTIVE Hereditary vitamin D resistant rickets (HVDRR) has been shown to be due to mutations in the gene encoding the vitamin D receptor (VDR). In two patients with the characteristic phenotype we have investigated the functional defect and sequenced the VDR cDNA. We report two new mutations in the DNA binding domain of the VDR gene and we have used the crystal‐lographic structure of the glucocorticold and oeltrogen receptors (GR and ER respectively) as models to explain the stereochemical… 

Identification of a novel mutation in hereditary vitamin D resistant rickets causing exon skipping

In a patient with characteristic features of this disorder, the functional defect was investigated and the coding region of the gene for mutations was sequenced.

Mutations in the vitamin D receptor gene in three kindreds associated with hereditary vitamin D resistant rickets.

Gel shift assays using nuclear extract from patient 3 demonstrated that the mutation that altered a conserved amino acid known to be involved in heterodimerization with other nuclear receptors affected protein: protein interactions.

Tryptophan Missense Mutation in the Ligand‐Binding Domain of the Vitamin D Receptor Causes Severe Resistance to 1,25‐Dihydroxyvitamin D

  • T. M. NguyenP. Adiceam M. Garabédian
  • Biology, Medicine
    Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
  • 2002
This case report of a new family with hereditary vitamin D‐ resistant rickets (HVDRR) emphasizes the crucial role of the VDR tryptophan for ligand binding and for transactivation of 1,25(OH)2D3 target genes.

A novel inborn error in the ligand-binding domain of the vitamin D receptor causes hereditary vitamin D-resistant rickets.

A novel mutation was identified in the VDR LBD that reduces VDR abundance and its affinity for 1,25(OH)(2)D(3) and interferes with RXRalpha heterodimerization resulting in the syndrome of HVDRR.

Hereditary 1,25‐Dihydroxyvitamin D–Resistant Rickets Due to an Opal Mutation Causing Premature Termination of the Vitamin D Receptor

The Arg30stop mutation truncates the VDR and leads to a hormone‐resistant condition which is the molecular basis of HVDRR in this patient.

Vitamin D receptor mutations in patients with hereditary 1,25-dihydroxyvitamin D-resistant rickets.

A novel mutation in helix 12 of the vitamin D receptor impairs coactivator interaction and causes hereditary 1,25-dihydroxyvitamin D-resistant rickets without alopecia.

The first case of a naturally occurring mutation in the VDR (E420K) that disrupts coactivator binding to theVDR and causes HVDRR is identified.

Molecular Defects in the Vitamin D Receptor Associated with Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets (HVDRR)

Children with HVDRR have been successfully treated with intravenous calcium that bypasses the intestinal defect in calcium transport due to the lack of 1,25(OH)2D action on the mutant VDR.

Hereditary Resistance to Vitamin D

This chapter will describe the clinical manifestations of HVDRR and the genetic defects in the VDR that result in this hormone-resistant syndrome.
...

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