Document Detail

A single-base substitution in the proximal Sp1 site of the human low density lipoprotein receptor promoter as a cause of heterozygous familial hypercholesterolemia.
MedLine Citation:
PMID:  7937987     Owner:  NLM     Status:  MEDLINE    
We have identified a Finnish family with a typical phenotype of heterozygous familial hypercholesterolemia (FH) due to a single-base substitution in the proximal Sp1 binding site of the low density lipoprotein (LDL) receptor gene promoter. The mutation, a C-->T substitution at nucleotide -43, cosegregated with the FH phenotype in six available family members and abolished binding of Sp1 transcription factor to this site. As a consequence, transcriptional activity of the mutated LDL receptor promoter was only about 1/20th of that of the wild-type promoter, as judged by transfection studies in HeLa cells. Studies of primary fibroblast cultures established from a family member revealed a markedly reduced LDL receptor mRNA concentration as well as reduction of binding, internalization, and degradation of 125I-labeled LDL to values < 50% of those in normal fibroblasts. This DNA alteration is thus a naturally occurring promoter mutation causing a severe disorder of human lipoprotein metabolism.
U M Koivisto; J J Palvimo; O A Jänne; K Kontula
Related Documents :
9632647 - Human monocyte-derived macrophages secrete two forms of proteoglycan-macrophage colony-...
11060347 - Human apolipoprotein e7:lysine mutations in the carboxy-terminal domain are directly re...
2542277 - Human apolipoprotein e. receptor binding activity of truncated variants with carboxyl-t...
18031277 - Stabilization of the active form(s) of human paraoxonase by human phosphate-binding pro...
15537757 - Modulation of the ligand binding properties of the transcription repressor nmra by gata...
3734667 - Circulating insulin-like growth factor-binding proteins in fetal, neonatal and adult sh...
Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  91     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1994 Oct 
Date Detail:
Created Date:  1994-11-23     Completed Date:  1994-11-23     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  10526-30     Citation Subset:  IM    
Institute of Biotechnology, University of Helsinki, Finland.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Base Sequence
Binding Sites
Cell Line
Cells, Cultured
Cercopithecus aethiops
Chloramphenicol O-Acetyltransferase / analysis,  biosynthesis
DNA / genetics,  metabolism
DNA Primers
Deoxyribonuclease I
Fibroblasts / metabolism
Hela Cells
Hyperlipoproteinemia Type II / genetics*,  metabolism
Middle Aged
Molecular Sequence Data
Point Mutation*
Polymerase Chain Reaction
Promoter Regions, Genetic*
RNA, Messenger / analysis,  biosynthesis
Receptors, LDL / biosynthesis,  genetics*
Restriction Mapping
Skin / metabolism
Sp1 Transcription Factor / metabolism*
Reg. No./Substance:
0/DNA Primers; 0/Oligodeoxyribonucleotides; 0/RNA, Messenger; 0/Receptors, LDL; 0/Sp1 Transcription Factor; 9007-49-2/DNA; EC O-Acetyltransferase; EC I

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Topological analysis of the human beta 2-adrenergic receptor expressed in Escherichia coli.
Next Document:  Dominant lethal mutations in the plasma membrane H(+)-ATPase gene of Saccharomyces cerevisiae.