Cargando…

Identification of Two Novel Fibrinogen Bβ Chain Mutations in Two Slovak Families with Quantitative Fibrinogen Disorders

Congenital fibrinogen disorders are caused by mutations in one of the three fibrinogen genes that affect the synthesis, assembly, intracellular processing, stability or secretion of fibrinogen. Functional studies of mutant Bβ-chains revealed the importance of individual residues as well as three-dim...

Descripción completa

Detalles Bibliográficos
Autores principales: Simurda, Tomas, Zolkova, Jana, Snahnicanova, Zuzana, Loderer, Dusan, Skornova, Ingrid, Sokol, Juraj, Hudecek, Jan, Stasko, Jan, Lasabova, Zora, Kubisz, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796050/
https://www.ncbi.nlm.nih.gov/pubmed/29286337
http://dx.doi.org/10.3390/ijms19010100
_version_ 1783297421202161664
author Simurda, Tomas
Zolkova, Jana
Snahnicanova, Zuzana
Loderer, Dusan
Skornova, Ingrid
Sokol, Juraj
Hudecek, Jan
Stasko, Jan
Lasabova, Zora
Kubisz, Peter
author_facet Simurda, Tomas
Zolkova, Jana
Snahnicanova, Zuzana
Loderer, Dusan
Skornova, Ingrid
Sokol, Juraj
Hudecek, Jan
Stasko, Jan
Lasabova, Zora
Kubisz, Peter
author_sort Simurda, Tomas
collection PubMed
description Congenital fibrinogen disorders are caused by mutations in one of the three fibrinogen genes that affect the synthesis, assembly, intracellular processing, stability or secretion of fibrinogen. Functional studies of mutant Bβ-chains revealed the importance of individual residues as well as three-dimensional structures for fibrinogen assembly and secretion. This study describes two novel homozygous fibrinogen Bβ chain mutations in two Slovak families with afibrinogenemia and hypofibrinogenemia. Peripheral blood samples were collected from all subjects with the aim of identifying the causative mutation. Coagulation-related tests and rotational thromboelastometry were performed. All exons and exon–intron boundaries of the fibrinogen genes (FGA, FGB and FGG) were amplified by PCR followed by direct sequencing. Sequence analysis of the three fibrinogen genes allowed us to identify two novel homozygous mutations in the FGB gene. A novel Bβ chain truncation (BβGln180Stop) was detected in a 28-year-old afibrinogenemic man with bleeding episodes including repeated haemorrhaging into muscles, joints, and soft tissues, and mucocutaneous bleeding and a novel Bβ missense mutation (BβTyr368His) was found in a 62-year-old hypofibrinogenemic man with recurrent deep and superficial venous thromboses of the lower extremities. The novel missense mutation was confirmed by molecular modelling. Both studying the molecular anomalies and the modelling of fibrinogenic mutants help us to understand the extremely complex machinery of fibrinogen biosynthesis and finally better assess its correlation with the patient’s clinical course.
format Online
Article
Text
id pubmed-5796050
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-57960502018-02-09 Identification of Two Novel Fibrinogen Bβ Chain Mutations in Two Slovak Families with Quantitative Fibrinogen Disorders Simurda, Tomas Zolkova, Jana Snahnicanova, Zuzana Loderer, Dusan Skornova, Ingrid Sokol, Juraj Hudecek, Jan Stasko, Jan Lasabova, Zora Kubisz, Peter Int J Mol Sci Article Congenital fibrinogen disorders are caused by mutations in one of the three fibrinogen genes that affect the synthesis, assembly, intracellular processing, stability or secretion of fibrinogen. Functional studies of mutant Bβ-chains revealed the importance of individual residues as well as three-dimensional structures for fibrinogen assembly and secretion. This study describes two novel homozygous fibrinogen Bβ chain mutations in two Slovak families with afibrinogenemia and hypofibrinogenemia. Peripheral blood samples were collected from all subjects with the aim of identifying the causative mutation. Coagulation-related tests and rotational thromboelastometry were performed. All exons and exon–intron boundaries of the fibrinogen genes (FGA, FGB and FGG) were amplified by PCR followed by direct sequencing. Sequence analysis of the three fibrinogen genes allowed us to identify two novel homozygous mutations in the FGB gene. A novel Bβ chain truncation (BβGln180Stop) was detected in a 28-year-old afibrinogenemic man with bleeding episodes including repeated haemorrhaging into muscles, joints, and soft tissues, and mucocutaneous bleeding and a novel Bβ missense mutation (BβTyr368His) was found in a 62-year-old hypofibrinogenemic man with recurrent deep and superficial venous thromboses of the lower extremities. The novel missense mutation was confirmed by molecular modelling. Both studying the molecular anomalies and the modelling of fibrinogenic mutants help us to understand the extremely complex machinery of fibrinogen biosynthesis and finally better assess its correlation with the patient’s clinical course. MDPI 2017-12-29 /pmc/articles/PMC5796050/ /pubmed/29286337 http://dx.doi.org/10.3390/ijms19010100 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Simurda, Tomas
Zolkova, Jana
Snahnicanova, Zuzana
Loderer, Dusan
Skornova, Ingrid
Sokol, Juraj
Hudecek, Jan
Stasko, Jan
Lasabova, Zora
Kubisz, Peter
Identification of Two Novel Fibrinogen Bβ Chain Mutations in Two Slovak Families with Quantitative Fibrinogen Disorders
title Identification of Two Novel Fibrinogen Bβ Chain Mutations in Two Slovak Families with Quantitative Fibrinogen Disorders
title_full Identification of Two Novel Fibrinogen Bβ Chain Mutations in Two Slovak Families with Quantitative Fibrinogen Disorders
title_fullStr Identification of Two Novel Fibrinogen Bβ Chain Mutations in Two Slovak Families with Quantitative Fibrinogen Disorders
title_full_unstemmed Identification of Two Novel Fibrinogen Bβ Chain Mutations in Two Slovak Families with Quantitative Fibrinogen Disorders
title_short Identification of Two Novel Fibrinogen Bβ Chain Mutations in Two Slovak Families with Quantitative Fibrinogen Disorders
title_sort identification of two novel fibrinogen bβ chain mutations in two slovak families with quantitative fibrinogen disorders
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796050/
https://www.ncbi.nlm.nih.gov/pubmed/29286337
http://dx.doi.org/10.3390/ijms19010100
work_keys_str_mv AT simurdatomas identificationoftwonovelfibrinogenbbchainmutationsintwoslovakfamilieswithquantitativefibrinogendisorders
AT zolkovajana identificationoftwonovelfibrinogenbbchainmutationsintwoslovakfamilieswithquantitativefibrinogendisorders
AT snahnicanovazuzana identificationoftwonovelfibrinogenbbchainmutationsintwoslovakfamilieswithquantitativefibrinogendisorders
AT lodererdusan identificationoftwonovelfibrinogenbbchainmutationsintwoslovakfamilieswithquantitativefibrinogendisorders
AT skornovaingrid identificationoftwonovelfibrinogenbbchainmutationsintwoslovakfamilieswithquantitativefibrinogendisorders
AT sokoljuraj identificationoftwonovelfibrinogenbbchainmutationsintwoslovakfamilieswithquantitativefibrinogendisorders
AT hudecekjan identificationoftwonovelfibrinogenbbchainmutationsintwoslovakfamilieswithquantitativefibrinogendisorders
AT staskojan identificationoftwonovelfibrinogenbbchainmutationsintwoslovakfamilieswithquantitativefibrinogendisorders
AT lasabovazora identificationoftwonovelfibrinogenbbchainmutationsintwoslovakfamilieswithquantitativefibrinogendisorders
AT kubiszpeter identificationoftwonovelfibrinogenbbchainmutationsintwoslovakfamilieswithquantitativefibrinogendisorders