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Titolo:
CHARACTERIZATION OF A SPLICE-SITE MUTATION IN THE GENE FOR THE LDL RECEPTOR-ASSOCIATED WITH AN UNPREDICTABLY SEVERE CLINICAL PHENOTYPE IN ENGLISH PATIENTS WITH HETEROZYGOUS FH
Autore:
SUN XM; PATEL DD; BHATNAGAR D; KNIGHT BL; SOUTAR AK;
Indirizzi:
HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,MRC,CTR CLIN SCI,LIPOPROT TEAM,DU CANE RD LONDON W12 0NN ENGLAND HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,MRC,CTR CLIN SCI,LIPOPROT TEAM LONDON W12 0NN ENGLAND MANCHESTER ROYAL INFIRM,DEPT MED MANCHESTER M13 9WL LANCS ENGLAND
Titolo Testata:
Arteriosclerosis, thrombosis, and vascular biology
fascicolo: 2, volume: 15, anno: 1995,
pagine: 219 - 227
SICI:
1079-5642(1995)15:2<219:COASMI>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
LOW-DENSITY-LIPOPROTEIN; HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA; DNA POLYMORPHISM; POINT MUTATIONS; BINDING; LOCUS; AMPLIFICATION; RECOMBINATION; CHOLESTEROL; DEGRADATION;
Keywords:
MUTANT PROTEIN; IMMUNOBLOTTING; LDL BINDING; SINGLE-STRAND CONFORMATIONAL POLYMORPHISM; IN VITRO EXPRESSION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
39
Recensione:
Indirizzi per estratti:
Citazione:
X.M. Sun et al., "CHARACTERIZATION OF A SPLICE-SITE MUTATION IN THE GENE FOR THE LDL RECEPTOR-ASSOCIATED WITH AN UNPREDICTABLY SEVERE CLINICAL PHENOTYPE IN ENGLISH PATIENTS WITH HETEROZYGOUS FH", Arteriosclerosis, thrombosis, and vascular biology, 15(2), 1995, pp. 219-227

Abstract

We have identified a substitution of G to A in the first base pair ofintron 3 in the LDL receptor gene of an English heterozygous familialhypercholesterolemia (FH) patient. Reverse transcription, amplification, and nucleotide sequencing of the LDL receptor mRNA from mononuclear blood cells showed both the normal mRNA and one that lacked the nucleotides encoded by exon 3, which codes for repeat 2 of the ligand-binding domain. The same mutant allele was identified in 2/200 unrelated FH patients from the London area and 4/77 from Manchester. Immunoblotting of cultured lymphoblasts from the index patient revealed the normalreceptor protein and smaller amounts of a receptor protein with electrophoretic mobility consistent with a deletion of the 41 amino acid residues encoded by exon 3. Normal amounts of a similar protein were observed when the mutant cDNA was expressed in heterologous cells; this protein showed reduced binding affinity for LDL but bound apoprotein E-containing lipoproteins normally. Despite these and other observationsthat repeat 2 of the binding domain is relatively unimportant for receptor function in vitro, carriers of this allele exhibit a severe clinical phenotype, typical of FH. Thus, the relationship between genotypeand phenotype in heterozygous FH is not always predictable.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 13:04:52