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Titre du document / Document title

F X Nottingham and F X Taunton two novel mutations in Factor X resulting in loss of functional activity and an interpretation using molecular modelling

Auteur(s) / Author(s)

DEAM S. (1) ; SRINIVASAN N. (2) ; WESTBY J. (1) ; HORN E. H. (3) ; DOLAN G. (1) ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

(1) Departments of Haematology and Clinical Chemistry, Queen's Medical Centre, Nottingham, ROYAUME-UNI
(2) Molecular Biophysics Unit, Indian Institute of Science, Bangalore, INDE
(3) Department of Haematology, Royal Infirmary, Edinburgh, ROYAUME-UNI

Résumé / Abstract

We report two novel mutations in the Factor X gene which result in a bleeding tendency in two unrelated Caucasian families. Although the mutations occur at adjacent codons in exon 8 and result in reduced functional activity with normal antigen levels, the patterns of inheritance appear to be quite distinct. Factor X Nottingham (alanine 404 threonine) appears to be associated with an autosomal recessive pattern of inheritance. In contrast, Factor X Taunton (arginine 405 glycine) results in a mode of inheritance consistent with an autosomal dominant pattern, all five of the heterozygotes in this family being clinically affected. Molecular modelling studies suggest that, in the case of Factor X Nottingham, a drastic conformational change causes major unfolding of the protein. For Factor X Taunton, less extreme conformational changes occur causing loss of functional activity such that substrate binding sites might be maintained. It is proposed that competition with wild type for substrate binding could occur leading to a dominant negative effect.

Revue / Journal Title

Thrombosis and haemostasis    ISSN  0340-6245   CODEN THHADQ 

Source / Source

2001, vol. 85, no2, pp. 265-269 (23 ref.)

Langue / Language

Anglais

Editeur / Publisher

Schattauer, Stuttgart, ALLEMAGNE  (1976) (Revue)

Mots-clés anglais / English Keywords

Deficiency

;

Coagulation factor

;

Factor X

;

Human

;

Female

;

Case study

;

Family study

;

Mutation

;

Gene

;

Biological activity

;

Molecular structure

;

Modeling

;

Hemopathy

;

Coagulopathy

;

Genetics

;

Congenital disease

;

Mots-clés français / French Keywords

Déficit

;

Facteur coagulation

;

Facteur Stuart

;

Homme

;

Femelle

;

Etude cas

;

Etude familiale

;

Mutation

;

Gène

;

Activité biologique

;

Structure moléculaire

;

Modélisation

;

Facteur X Nottingham

;

Facteur X Taunton

;

Hémopathie

;

Coagulopathie

;

Génétique

;

Maladie congénitale

;

Mots-clés espagnols / Spanish Keywords

Déficiencia

;

Factor coagulación

;

Factor Stuart

;

Hombre

;

Hembra

;

Estudio caso

;

Estudio familiar

;

Mutación

;

Gen

;

Actividad biológica

;

Estructura molecular

;

Modelización

;

Hemopatía

;

Coagulopatía

;

Genética

;

Enfermedad congénita

;

Localisation / Location

INIST-CNRS, Cote INIST : 10255, 35400009409880.0170

Nº notice refdoc (ud4) : 897961



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