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Titolo:
Molecular pathology of haemophilia A in Turkish patients: identification of 36 independent mutations
Autore:
Timur, AA; Gurgey, A; Aktuglu, G; Kavakli, K; Canatan, D; Olek, K; Caglayan, SH;
Indirizzi:
Bogazici Univ, Dept Mol Biol & Genet, TR-80815 Bebek, Turkey Bogazici Univ Bebek Turkey TR-80815 Biol & Genet, TR-80815 Bebek, Turkey Univ Hacettepe, Dept Paediat Hematol, TR-06100 Ankara, Turkey Univ Hacettepe Ankara Turkey TR-06100 t Hematol, TR-06100 Ankara, Turkey Univ Istanbul, Cerrahpasa Med Sch, Dept Hematol, Istanbul, Turkey Univ Istanbul Istanbul Turkey a Med Sch, Dept Hematol, Istanbul, Turkey Ege Univ, Dept Paediat Hematol, Izmir, Turkey Ege Univ Izmir TurkeyEge Univ, Dept Paediat Hematol, Izmir, Turkey State Hosp Antalya, Antalya, Turkey State Hosp Antalya Antalya TurkeyState Hosp Antalya, Antalya, Turkey Univ Bonn, Inst Klin Biochem, D-5300 Bonn, Germany Univ Bonn Bonn Germany D-5300 n, Inst Klin Biochem, D-5300 Bonn, Germany
Titolo Testata:
HAEMOPHILIA
fascicolo: 5, volume: 7, anno: 2001,
pagine: 475 - 481
SICI:
1351-8216(200109)7:5<475:MPOHAI>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
FACTOR-VIII GENE; GRADIENT GEL-ELECTROPHORESIS; SEVERE HEMOPHILIA-A; INVERSIONS; MODEL; POLYMORPHISMS; POPULATION; LEUKEMIA; MILD;
Keywords:
DGGE analysis; DNA sequencing; factor VIII gene; haemophilia A; mutation detection;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Caglayan, SH Bogazici Univ, Dept Mol Biol & Genet, TR-80815 Bebek, Turkey Bogazici Univ Bebek Turkey TR-80815 TR-80815 Bebek, Turkey
Citazione:
A.A. Timur et al., "Molecular pathology of haemophilia A in Turkish patients: identification of 36 independent mutations", HAEMOPHILIA, 7(5), 2001, pp. 475-481

Abstract

Haemophilia A is an X-linked recessive bleeding,disorder caused by heterogeneous mutations in the factor VIII gene. In an attempt to reveal the molecular pathology of Turkish haemophilia A patients, the coding sequence of the gene, excluding a large portion of exon 14, was amplified from genomic DNA and subjected to denaturing gradient gel electrophoresis prior to DNA sequencing. Fifty-nine haemophilia A patients were included in the study with severe, moderate and mild phenotypes observed in 24, 15 and 16 patients, respectively. Factor VIII activity and clinical phenotypes were not availablefor four patients. A total of 36 independent mutations were found, with a mutation detection efficacy of 61%. The mutations that were reported for the first time include 20 point mutations, one 8-bp insertion (TCAAGATA) in exon 4 and one large deletion greater than 2.8 kb involving exon 14. The novel point mutations were composed of three nonsense (Ser681-Ter, Cys2021Ter and Gln2113Ter), one splicing error (IVS-1G-->A), 15 missense mutations (Lys48Asn; Leu-98Phe; Thr118Ala; Cys248Tyr; Glu456Lys; Asp560Ala; Tyr664Cys; Phe679Leu; Gly691Trp; Asp1769His; Val1857Leu; Gly2026Gln; Arg2163-Pro; Asp2288Ala; and Arg2304Leu) and a T deletion in exon 25 that caused a frameshiftfollowed by a stop codon. All missense mutations except Val1857Leu, which maintained a conserved nonpolar R group, occurred at amino acids conserved among four species and were most probably pathogenic. In addition, two sequence changes (IVS3-9C-->T) and (Leu2230Leu) were also detected in patients carrying Val1857Leu and Phe679Leu missense mutations, respectively. Identification of mutation origins in eight sporadic cases revealed an equal sex ratio of mutations.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 14/07/20 alle ore 13:01:52