Titre
Protein modelling to understand FGB mutations leading to congenital hypofibrinogenaemia.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Casini, A.
Auteure/Auteur
Vilar, R.
Auteure/Auteur
Beauverd, Y.
Auteure/Auteur
Aslan, D.
Auteure/Auteur
Devreese, K.
Auteure/Auteur
Mondelaers, V.
Auteure/Auteur
Alberio, L.
Auteure/Auteur
Gubert, C.
Auteure/Auteur
de Moerloose, P.
Auteure/Auteur
Neerman-Arbez, M.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1365-2516
Statut éditorial
Publié
Date de publication
2017-07
Volume
23
Numéro
4
Première page
583
Dernière page/numéro d’article
589
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Case Reports ; Journal Article
Publication Status: ppublish
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.
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.
PID Serval
serval:BIB_46D3108BBF44
PMID
Date de création
2017-03-28T16:25:10.719Z
Date de création dans IRIS
2025-05-20T14:58:08Z