Document Detail


Molecular genetics of quantitative fibrinogen disorders.
MedLine Citation:
PMID:  17430139     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Fibrinogen is a complex glycoprotein involved in the final step of the coagulation cascade as the precursor of fibrin monomers that participate in the formation of the haemostatic plug. Three genes (FGA, FGB, and FGG) clustered on chromosome 4q31.3-4q32.1 encode the three polypeptide chains (Aalpha, Bbeta, and gamma), which in a pairwise fashion form the hexameric circulating molecule. Among congenital fibrinogen deficiencies, quantitative defects (also called type I deficiencies; i.e. congenital afibrino-genemia [CAF] and hypofibrinogenemia) are characterized by the concomitant absence or reduction of coagulant activity and immunoreactive protein, while qualitative defects (type II deficiencies; i.e. dysfibrinogenemia and hypodysfibrino-genemia) show low clotting protein in contrast with normal or moderately reduced antigen. Patients affected by CAF (Mendelian Inheritance in Man, [MIM] #202400) or severe hypofibrinogenemia (MIM+134820, *134830, and *134850) may experience bleeding manifestations varying from mild to catastrophic. Although many cases of fibrinogen deficiencies have been described from a clinical point of view, only in a minority of cases the causal mutation was identified. The genetic defects so far described, most unique for any analyzed family, are invariantly located in the fibrinogen cluster; for only few of them the pathogenic role either at the protein or at the mRNA level has been investigated. This review, besides providing a concise description of the main structural and functional properties of fibrinogen and giving an overview of the clinical manifestations, the laboratory diagnosis and therapeutic approches, will be focused on the present knowledge on the genetic basis of quantitative fibrinogen deficiencies. Our systematic analysis of the available clinical and genetic data on these disorders evidences their high allelic heterogeneity, the existence of different pathogenic mechanisms, and the absence of strong genotype/phenotype correlations.
Authors:
R Asselta; S Spena; S Duga; M L Tenchini
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Cardiovascular & hematological agents in medicinal chemistry     Volume:  5     ISSN:  1871-5257     ISO Abbreviation:  -     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-04-13     Completed Date:  2007-05-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101266881     Medline TA:  Cardiovasc Hematol Agents Med Chem     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  163-73     Citation Subset:  IM    
Affiliation:
Department of Biology and Genetics for Medical Sciences, University of Milan, Via Viotti, 3/5 -20133 Milano, Italy. rosanna.asselta@unimi.it
Data Bank Information
Bank Name/Acc. No.:
OMIM/134820;  134830;  134850;  202400
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MeSH Terms
Descriptor/Qualifier:
Afibrinogenemia / blood,  genetics*
Blood Coagulation Tests
Fibrinogen / chemistry,  genetics*
Genotype
Hemorrhage
Humans
Mutation* / genetics,  physiology
Phenotype
Protein Structure, Secondary
Chemical
Reg. No./Substance:
9001-32-5/Fibrinogen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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