Linked Life Data

7852500

Source:http://linkedlifedata.com/resource/pubmed/id/7852500

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1995-3-10
pubmed:abstractText
Corticosterone methyloxidase type I (CMO-I) deficiency is an autosomal recessively inherited disorder causing congenital hypoaldosteronism due to defects in aldosterone synthase (P450aldo), the enzyme that converts 11-deoxycorticosterone to corticosterone, 18-hydroxycorticosterone, and aldosterone. To clarify the molecular basis of CMO-I deficiency and gain further insight into the structure-function relationship of P450aldo, we cloned and sequenced the CYP11B2 gene (encoding P450aldo) of a male Caucasian patient suffering from CMO-I deficiency and identified a single point mutation leading to substitution of the highly conserved arginine-384 by proline (R384P). Differential hybridization of mutation-specific oligonucleotide probes to polymerase chain reaction-amplified CYP11B2 fragments revealed that both parents were heterozygous carriers for R384P, whereas the patient appeared homozygous. The patient's healthy brother and 85 individuals without known aldosterone synthase deficiency did not carry the R384P mutation. Introduction of this mutation into a CYP11B2 complementary DNA expression vector construct and subsequent expression in COS cells revealed that R384P leads to complete loss of 11 beta- and 18-hydroxylase activities of P450aldo. Thus, the R384P mutation provides a molecular explanation for the CMO-I deficiency in this patient and suggests that arginine-384 plays a major role in P450aldo function.
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
80
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
424-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Amino acid substitution R384P in aldosterone synthase causes corticosterone methyloxidase type I deficiency.
pubmed:affiliation
Department of Molecular Biology, Institute for General and Experimental Pathology, University of Innsbruck Medical School, Austria.
pubmed:publicationType
Journal Article, Case Reports, Research Support, Non-U.S. Gov't