Protein modelling to understand FGB mutations leading to congenital hypofibrinogenaemia.

Détails

ID Serval
serval:BIB_46D3108BBF44
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Protein modelling to understand FGB mutations leading to congenital hypofibrinogenaemia.
Périodique
Haemophilia
Auteur(s)
Casini A., Vilar R., Beauverd Y., Aslan D., Devreese K., Mondelaers V., Alberio L., Gubert C., de Moerloose P., Neerman-Arbez M.
ISSN
1365-2516 (Electronic)
ISSN-L
1351-8216
Statut éditorial
Publié
Date de publication
07/2017
Peer-reviewed
Oui
Volume
23
Numéro
4
Pages
583-589
Langue
anglais
Notes
Publication types: Case Reports ; Journal Article
Publication Status: ppublish
Résumé
Congenital hypofibrinogenaemia is a quantitative fibrinogen disorder characterized by proportionally decreased levels of functional and antigenic fibrinogen. Mutations accounting for quantitative fibrinogen disorders are relatively frequent in the conserved COOH-terminal globular domains of the γ and Bβ chains. The latter mutations are of particular interest since the Bβ-chain is considered the rate-limiting chain in the hepatic production of the fibrinogen hexamer.
The aim of this study was to study the molecular pattern of four patients with congenital hypofibrinogenaemia.
Four novel fibrinogen Bβ-chain mutations leading to congenital hypofibrinogenaemia were identified in four women with heterogeneous symptoms. The human fibrinogen beta chain precursor protein sequence (P02675) was obtained from the UniProt database. The resulting models were analysed using swisspdbviewer 4.1.0.
Three patients were heterozygous for different missense mutations located in the highly conserved β nodule: c.882G>C:Arg294Ser (Arg264Ser), c.1298G>T:Trp433Leu (Trp403Leu) and c.1329C>G:Asn443Lys (Asn413Lys). Modelling analyses predicted major structural modifications likely to result in impaired fibrinogen secretion. One patient was heterozygous for an intron 7 donor splice mutation (c.1244 + 1G>A), leading to the complete abolishment of the donor site.
Protein modelling of new causative mutations and comparison of molecular, biochemical and clinical data continue to yield valuable information on the development and course of fibrinogen disorders as well as on the choice of the most appropriate treatments.

Mots-clé
Adolescent, Adult, Afibrinogenemia/genetics, Child, Female, Fibrinogen/chemistry, Fibrinogen/genetics, Heterozygote, Humans, Models, Molecular, Mutation, Protein Structure, Secondary, bleeding, congenital fibrinogen disorders, hypofibrinogenaemia, mutation, thrombosis
Pubmed
Web of science
Création de la notice
28/03/2017 18:25
Dernière modification de la notice
22/03/2018 22:05
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