Publication Date:
1988-12-23
Description:
Hypocalcemic vitamin D-resistant rickets is a human genetic disease resulting from target organ resistance to the action of 1,25-dihydroxyvitamin D3. Two families with affected children homozygous for this autosomal recessive disorder were studied for abnormalities in the intracellular vitamin D receptor (VDR) and its gene. Although the receptor displays normal binding of 1,25-dihydroxyvitamin D3 hormone, VDR from affected family members has a decreased affinity for DNA. Genomic DNA isolated from these families was subjected to oligonucleotide-primed DNA amplification, and each of the nine exons encoding the receptor protein was sequenced for a genetic mutation. In each family, a different single nucleotide mutation was found in the DNA binding domain of the protein; one family near the tip of the first zinc finger (Gly----Asp) and one at the tip of the second zinc finger (Arg----Gly). The mutant residues were created in vitro by oligonucleotide directed point mutagenesis of wild-type VDR complementary DNA and this cDNA was transfected into COS-1 cells. The produced protein is biochemically indistinguishable from the receptor isolated from patients.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hughes, M R -- Malloy, P J -- Kieback, D G -- Kesterson, R A -- Pike, J W -- Feldman, D -- O'Malley, B W -- New York, N.Y. -- Science. 1988 Dec 23;242(4886):1702-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2849209" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Animals
;
Binding Sites
;
Calcitriol/metabolism
;
Cell Line
;
Cell Line, Transformed
;
Codon
;
DNA/genetics/metabolism
;
Exons
;
Female
;
Gene Amplification
;
Homozygote
;
Humans
;
Hypocalcemia/*genetics
;
Immunoblotting
;
Male
;
Molecular Sequence Data
;
*Mutation
;
Receptors, Calcitriol
;
Receptors, Steroid/*genetics/metabolism
;
Rickets/*genetics
;
Transfection
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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