Linked Life Data

9012641

Source:http://linkedlifedata.com/resource/pubmed/id/9012641

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1997-2-25
pubmed:abstractText
We have identified a large kindred with severe serum HDL cholesterol deficiency. The proband, a 65-year-old woman, had greatly diminished concentrations of serum HDL cholesterol (0.19 mmol/L) and apolipoprotein (apo) A-I (21.9 mg/dL). HDL cholesterol and apo A-I levels were similarly reduced in all affected family members, while apo A-II levels were about half of those in the nonaffected family members. Pedigree analysis suggested a dominant inheritance pattern of the phenotype. Sequence analysis of the exons and exon-intron boundaries of the apo A-I gene revealed heterozygosity for a single T-to-G point mutation substituting arginine for leucine at residue 159 of the mature apo A-I protein (apo A-IFin). The T-to-G substitution destroys an Fsp I cleavage site, permitting direct polymerase chain reaction/restriction enzyme analysis of the mutation. All the affected family members were shown to be heterozygous for the apo A-IFin mutation. Isoelectric focusing revealed the presence of the mutant apo A-IFin protein in both serum and HDL of the affected subjects. Functional consequences of the mutation were examined by expressing the mutated and wild-type apo A-I cDNAs in COS-7 cells. The mutant apo A-I mRNA had a size similar to that of the normal mRNA, and both mutant and wild-type apo A-I proteins were secreted into the cell media. In vivo kinetic studies of apo A-I revealed increased catabolism in affected subjects. In conclusion, we describe a novel point mutation of the apo A-I gene, apo A-IFin, causing a dominantly negative phenotype as regards serum HDL levels, possibly due to increased catabolism of apo A-I.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1079-5642
pubmed:author
pubmed:issnType
Print
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
83-90
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Apolipoprotein A-IFin. Dominantly inherited hypoalphalipoproteinemia due to a single base substitution in the apolipoprotein A-I gene.
pubmed:affiliation
Institute of Biotechnology, University of Helsinki, Finland. helena.miettinen@hyks.mailnet.fi
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't