Linked Life Data

2537329

Source:http://linkedlifedata.com/resource/pubmed/id/2537329

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1989-3-27
pubmed:abstractText
Vitamin D-dependent rickets, type II, is a hereditary disease that results from target organ resistance to the action of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. We describe here a family (designated G) with a defect in the DNA-binding domain of the 1,25-(OH)2D receptor (VDR) manifested by normal steroid binding and decreased VDR affinity for DNA. The phenotypically normal parents are heterozygous, expressing both normal and defective forms of VDR. The affected children in this family had early-onset rickets, alopecia, hypocalcemia, and elevated serum 1,25-(OH)2D3 levels. The VDR of cultured skin fibroblasts of the affected children (G1 and G2) as well as the parents (G3 and G4) bound [3H]1,25-(OH)2D3 normally (Kd = 2-3 X 10(-11) mol/L; maximal number of binding sites = 20-40 fmol/mg protein). The cells from G1 and G2 were resistant to 1,25-(OH)2D3 action, as measured by induction of 24-hydroxylase activity, while the cells from G3 and G4 responded normally. Western blot analysis using the anti-VDR monoclonal antibody 9A7 showed that hypertonic extracts of fibroblasts from both affected children (G1 and G2) and their parents (G3 and G4) had immunoreactive bands of 48K, identical to the size of the VDR in normal cells. The VDR from G1 and G2 eluted as a single peak from DNA-cellulose columns at a lower salt concentration (0.1 mol/L) than that from normal subjects (0.2 mol/L), indicating an apparent decreased affinity for DNA. Fibroblast VDR from G3 and G4 each eluted from DNA-cellulose columns as two peaks, the normal peak (0.2 mol/L) and the abnormal peak (0.1 mol/L), which was found in G1 and G2. Western blot analysis of the 0.1 and 0.2 mol/L KCl peak fractions also confirmed that VDR was present in only the 0.1 mol/L fraction and not the 0.2 mol/L fraction from G1. However, VDR was present in both fractions from G3. In summary, this vitamin D-dependent rickets, type II, kindred has a defect in the DNA-binding domain of VDR. The parents are phenotypically normal and express both the normal and defective VDR alleles, as demonstrated by both DNA-cellulose chromatography and Western blot analysis. The affected children are resistant to 1,25-(OH)2D3 action and are homozygous for the defective VDR.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-972X
pubmed:author
pubmed:issnType
Print
pubmed:volume
68
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
263-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Abnormal binding of vitamin D receptors to deoxyribonucleic acid in a kindred with vitamin D-dependent rickets, type II.
pubmed:affiliation
Department of Medicine, Stanford University School of Medicine, California 94305.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't