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Titolo:
THE GENETIC-DEFECT IN 2 WELL-STUDIED CASES OF BERNARD-SOULIER-SYNDROME - A POINT MUTATION IN THE 5TH LEUCINE-RICH REPEAT OF PLATELET GLYCOPROTEIN-IB-ALPHA
Autore:
LI CY; MARTIN SE; BOTH GJ;
Indirizzi:
VET ADM MED CTR,MED SERV,HEMATOL SECT,1660 S COLUMBIAN WAY SEATTLE WA98108 VET ADM MED CTR,MED SERV,HEMATOL SECT SEATTLE WA 98108 VET ADM MED CTR,RES SERV SEATTLE WA 98108 UNIV WASHINGTON SEATTLE WA 98195 MED CTR DELAWARE,DEPT MED NEWARK DE 00000 MED CTR DELAWARE,DEPT PATHOL NEWARK DE 00000 THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT MED PHILADELPHIA PA 19107
Titolo Testata:
Blood
fascicolo: 10, volume: 86, anno: 1995,
pagine: 3805 - 3814
SICI:
0006-4971(1995)86:10<3805:TGI2WC>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
VON-WILLEBRAND FACTOR; VONWILLEBRAND-FACTOR; GEL-ELECTROPHORESIS; ACID SEQUENCE; IX COMPLEX; MEMBRANE; LOCALIZATION; ADHESION; BINDING; BETA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
50
Recensione:
Indirizzi per estratti:
Citazione:
C.Y. Li et al., "THE GENETIC-DEFECT IN 2 WELL-STUDIED CASES OF BERNARD-SOULIER-SYNDROME - A POINT MUTATION IN THE 5TH LEUCINE-RICH REPEAT OF PLATELET GLYCOPROTEIN-IB-ALPHA", Blood, 86(10), 1995, pp. 3805-3814

Abstract

Bernard-Soulier syndrome (B-Ss) is a rare congenital bleeding disorder caused by abnormal giant platelets, thrombocytopenia, and defective glycoprotein (GP) Ib-V-IX, the adhesion receptor for von Willebrand factor (vWF), This report describes the molecular defect in two related individuals with well-established B-Ss whose platelets exhibit decreased GPIb-IX and normal GPV on their surfaces. The GPIb-V-IX genes of the two patients were analyzed by Southern blotting, hetero-duplex analysis, and polymerase chain reaction (PCR) amplification/sequencing. A point mutation was found in codon 129 of the GPIb alpha gene that results in the substitution of proline for leucine in the first position ofthe fifth leucine-rich glycoprotein repeat of the mature gene product. The mutation (CTC: leucine, wild-type to CCC:proline, mutant) eliminates a Sac I restriction site, facilitating analysis of the mutation in the propositi (both homozygotes), unaffected family members (8 heterozygotes and 8 wild-type), and 58 normal controls (116 wild-type alleles). The status of the genomes was confirmed by the sequencing of platelet cDNA, The mutation does not affect transcription of the Ib-IX genes, as estimated by PCR and Northern blot analysis, but it does inhibit surface expression of the receptor as assessed by transient transfection of mutant and wildtype GPIb alpha genes into mouse Ib beta-IX L cells. Many of the cells (43%) transfected with the normal gene expresssurface GPIb alpha, whereas untransfected cells and those transfectedwith the mutant gene lack surface GPIb alpha entirely. Patient platelets were tested both for VWF binding in the presence of ristocetin andfor surface GPIb-IX expression. In these instances, despite their inability to agglutinate with ristocetin and vWF, patient platelets exhibit about 40% of normal vWF binding and 40% of normal Ib-IX surface antigens. The results suggest that the described mutation (GPIb alpha: Leu129 --> Pro) affects the conformation of the GPIb-V-IX receptor, alters its availability on platelet surfaces, and causes the observed Bernard-Soulier phenotype. (C) 1995 by The American Society of Hematology.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/01/20 alle ore 12:43:16