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Titolo:
A MUTATION (T-45C) IN THE PROMOTER REGION OF THE LOW-DENSITY-LIPOPROTEIN (LDL)-RECEPTOR GENE IS ASSOCIATED WITH A MILD CLINICAL PHENOTYPE IN A PATIENT WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (FH)
Autore:
SUN XM; NEUWIRTH C; WADE DP; KNIGHT BL; SOUTAR AK;
Indirizzi:
HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,CTR CLIN SCI,MRC,LIPOPROT TEAM,DUCANE RD LONDON W12 0NN ENGLAND HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,CTR CLIN SCI,MRC,LIPOPROT TEAM LONDON W12 0NN ENGLAND
Titolo Testata:
Human molecular genetics
fascicolo: 11, volume: 4, anno: 1995,
pagine: 2125 - 2129
SICI:
0964-6906(1995)4:11<2125:AM(ITP>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
LDL RECEPTOR GENE; TRANSCRIPTION FACTOR; SEQUENCE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
14
Recensione:
Indirizzi per estratti:
Citazione:
X.M. Sun et al., "A MUTATION (T-45C) IN THE PROMOTER REGION OF THE LOW-DENSITY-LIPOPROTEIN (LDL)-RECEPTOR GENE IS ASSOCIATED WITH A MILD CLINICAL PHENOTYPE IN A PATIENT WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (FH)", Human molecular genetics, 4(11), 1995, pp. 2125-2129

Abstract

We have identified a rare mutation (T-45C) in the low density lipoprotein (LDL)-receptor gene in a Welsh patient with a clinical diagnosis of heterozygous familial hypercholesterolaemia (FH). The mutation is in the proximal Sp1 binding site in repeat 3 of the 42 bp region of thepromoter required for sterol-dependent regulation of transcription, but the substituted nucleotide is not a strongly conserved base in the consensus sequence for Sp1 binding. Normal and mutant promoter fragments (from base -600 to -5) were linked to a luciferase reporter gene, and transient expression in COS cells showed that the mutation reduced transcriptional activity to approximately 43% of normal in the presence, and 25% in the absence of sterols in the medium. Competitive gel-shift mobility assays showed that the mutation reduced the binding affinity for transcription factor Sp1. Analysis of a neutral polymorphism in the LDL-receptor mRNA from the patient's lymphoblasts showed that expression of one allele was reduced. Since Southern blotting of genomicDNA and sequencing of the entire coding region of the LDL-R gene did not reveal any other potential defects, we infer that the T-45 C mutation is the underlying cause of hypercholesterolaemia in the proband.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 15:56:04