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Titolo:
Symptomatic type 1 protein C deficiency caused by a de novo Ser270Leu mutation in the catalytic domain
Autore:
Lind, B; Koefoed, P; Thorsen, S;
Indirizzi:
Copenhagen Univ Hosp, Dept Clin Biochem, Sect Haemastasis & Thrombosis, Copenhagen, Denmark Copenhagen Univ Hosp Copenhagen Denmark Thrombosis, Copenhagen, Denmark
Titolo Testata:
BRITISH JOURNAL OF HAEMATOLOGY
fascicolo: 3, volume: 113, anno: 2001,
pagine: 642 - 648
SICI:
0007-1048(200106)113:3<642:ST1PCD>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
VENOUS THROMBOSIS; MISSENSE MUTATION; PROTHROMBIN GENE; MESSENGER-RNA; SEQUENCE; EVOLUTION; REGION; DNA;
Keywords:
protein C deficiency; de novo mutation; venous thromboembolism; serine proteinase; catalytic domain;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Lind, B Rigshosp, Dept Clin Biochem KB 3011, Sect Haemostasis & Thrombosis, Blegdamsvej 9, DK-2100 Copenhagen, Denmark Rigshosp Blegdamsvej 9 Copenhagen Denmark DK-2100 nhagen, Denmark
Citazione:
B. Lind et al., "Symptomatic type 1 protein C deficiency caused by a de novo Ser270Leu mutation in the catalytic domain", BR J HAEM, 113(3), 2001, pp. 642-648

Abstract

Heterozygosity for a C8524T transition in the protein C gene converting Ser270(T (C) under barG) to Leu(T (T) under barG) in the protease domain was identified in a family with venous thrombosis, The mutation was associated with parallel reduction in plasma levels of protein C anticoagulant activity and protein C antigen, which is consistent with a type 1 deficiency. Transient expression of mutant protein C cDNA in human kidney 293 cells and analysis of protein C antigen in culture media and cell lysates showed that the secretion of mutant protein compared with wild-type protein was reduced by at least 97% while the intracellular content of mutant and wild-type protein was similar, Northern blot analysis of total mRNA from transfected cells showed no reduction of the mutant protein C mRNA compared with wild-type protein C mRNA, Collectively, these results indicate that the Ser270Leu mutation in the affected family caused the plasma protein C deficiency and areconsistent with a disease mechanism that involves synthesis of mutant protein followed by intracellular degradation before its secretion into the extracellular space, The mutation was not present in the parents of the proband, suggesting a de novo mutation. Non-paternity was excluded after the analysis of three intragenic protein C polymorphisms and six dinucleotide repeat allele sets located in five different chromosomes.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 21:37:46