Linked Life Data

10320521

Source:http://linkedlifedata.com/resource/pubmed/id/10320521

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1999-6-15
pubmed:abstractText
Pseudovitamin D-defiency rickets (PDDR) is an autosomal recessive disorder characterized by hypocalcemia, rickets (which are resistant to treatment with vitamin D), and low or undetectable serum levels of 1,25-dihydroxyvitamin D (1,25(OH)2D). The symptoms are corrected with 1,25(OH)2D treatment, and the disease is now believed to result from a defect in the cytochrome P450 component (P450c1; CYP27B1) of the renal 25-hydroxyvitamin D-1alpha-hydroxylase (1-OHase). We have studied genomic DNA from three families with PDDR and have identified the same homozygous mutation in the P450c1 gene in two of the index cases, causing a frameshift in exon 8, resulting in a premature stop codon in the heme-binding domain. The two cases in the third kindred were compound heterozygotes with missense mutations in exons 6 and 9. We have also identified a C/T polymorphism in intron 6 of the P450c1 genomic DNA. Interferon gamma-inducible 1-OHase activity in blood-derived macrophages was shown by 1,25(OH)2D synthesis in all control cells tested (37-184 fmol/h/106 cells) and those from the PDDR family parents (34-116 fmol/h/106 cells) but was totally absent from the patients' cells, indicating a defect in their macrophage 1-OHase, similar to the presumed renal defect. The assumption of similarity between the renal and macrophage P450c1 was supported by our ability to clone a 514 bp sequence, including the heme-binding region of the macrophage P450c1 cDNA from controls, which was identical to that published for both the renal and keratinocyte P450c1 cDNAs.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0884-0431
pubmed:author
pubmed:issnType
Print
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
730-9
pubmed:dateRevised
2010-8-25
pubmed:meshHeading
pubmed-meshheading:10320521-24,25-Dihydroxyvitamin D 3, pubmed-meshheading:10320521-25-Hydroxyvitamin D3 1-alpha-Hydroxylase, pubmed-meshheading:10320521-Base Sequence, pubmed-meshheading:10320521-Cells, Cultured, pubmed-meshheading:10320521-Child, pubmed-meshheading:10320521-Child, Preschool, pubmed-meshheading:10320521-Chromosomes, Human, Pair 12, pubmed-meshheading:10320521-Cloning, Molecular, pubmed-meshheading:10320521-Cytochrome P-450 CYP27A1, pubmed-meshheading:10320521-Cytochrome P-450 Enzyme System, pubmed-meshheading:10320521-DNA, pubmed-meshheading:10320521-Female, pubmed-meshheading:10320521-Ferredoxins, pubmed-meshheading:10320521-Heme, pubmed-meshheading:10320521-Humans, pubmed-meshheading:10320521-Infant, pubmed-meshheading:10320521-Introns, pubmed-meshheading:10320521-Macrophages, pubmed-meshheading:10320521-Male, pubmed-meshheading:10320521-Molecular Sequence Data, pubmed-meshheading:10320521-Mutation, pubmed-meshheading:10320521-Pedigree, pubmed-meshheading:10320521-Polymorphism, Genetic, pubmed-meshheading:10320521-Rickets, pubmed-meshheading:10320521-Steroid Hydroxylases
pubmed:year
1999
pubmed:articleTitle
Novel mutations in the 1alpha-hydroxylase (P450c1) gene in three families with pseudovitamin D-deficiency rickets resulting in loss of functional enzyme activity in blood-derived macrophages.
pubmed:affiliation
University Department of Medicine, Manchester Royal Infirmary, Manchester, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't