Results

RDF/XMLNTriplesTurtleShow queryShare ▶
SubjectPredicateObject
http://purl.uniprot.org/citations/15842357http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/15842357http://www.w3.org/2000/01/rdf-schema#comment"

Background

Type I fibrinogen deficiencies (hypofibrinogenemia and afibrinogenemia) are rare congenital disorders characterized by low or unmeasurable plasma fibrinogen antigen levels. Their genetic bases are represented by mutations within the three fibrinogen genes. Among the 11 reported missense mutations, a few have been characterized by expression studies and found to have an impaired fibrinogen assembly and/or secretion. Histopathological analyses were previously reported in two hypofibrinogenemic cases with discernible hepatic disease, revealing that both underlying mutations (gamma-Gly284Arg and gamma-Arg375Trp) were associated with hepatic fibrinogen endoplasmic reticulum storage disease (ERSD).

Objective

The objective of this study was to investigate the liver histology in an afibrinogenemic patient, homozygous for the Bbeta-Leu353Arg mutation, and to study the intracellular processing of the mutant protein.

Patients and methods

Liver histology was evaluated by light microscopy, electron microscopy and immunocytochemistry. Intracellular processing of mutant fibrinogen was analyzed by pulse-chase labeling and immunoprecipitation experiments. Messenger RNA levels were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR).

Results

The histopathological characterization of the liver showed no signs of fibrinogen accumulation, a difference from the previously reported findings in two hypofibrinogenemic kindreds with ERSD. To evaluate whether the Bbeta-Leu353Arg mutation and the ERSD-associated gamma-Gly284Arg mutation affected intracellular fibrinogen trafficking differently, both mutant proteins were expressed in COS-1 cells. Bbeta-Leu353Arg led to a more severe secretion defect, but no differences that could explain phenotype-genotype correlation were found in the intracellular processing. Endoglycosidase-H analysis demonstrated a secretion block before translocation to the Golgi medial stacks. Real-time RT-PCR studies showed normal levels of the Bbeta mRNA in the patient's liver.

Conclusions

The results confirm that Bbeta-Leu353Arg is associated with impaired fibrinogen secretion, but not with hepatic ERSD."xsd:string
http://purl.uniprot.org/citations/15842357http://purl.org/dc/terms/identifier"doi:10.1111/j.1538-7836.2005.01229.x"xsd:string
http://purl.uniprot.org/citations/15842357http://purl.uniprot.org/core/author"Asselta R."xsd:string
http://purl.uniprot.org/citations/15842357http://purl.uniprot.org/core/author"Duga S."xsd:string
http://purl.uniprot.org/citations/15842357http://purl.uniprot.org/core/author"Malcovati M."xsd:string
http://purl.uniprot.org/citations/15842357http://purl.uniprot.org/core/author"Tenchini M.L."xsd:string
http://purl.uniprot.org/citations/15842357http://purl.uniprot.org/core/author"Pellegrini C."xsd:string
http://purl.uniprot.org/citations/15842357http://purl.uniprot.org/core/author"Santagostino E."xsd:string
http://purl.uniprot.org/citations/15842357http://purl.uniprot.org/core/author"Maggioni M."xsd:string
http://purl.uniprot.org/citations/15842357http://purl.uniprot.org/core/author"Coggi G."xsd:string
http://purl.uniprot.org/citations/15842357http://purl.uniprot.org/core/author"Braidotti P."xsd:string
http://purl.uniprot.org/citations/15842357http://purl.uniprot.org/core/date"2005"xsd:gYear
http://purl.uniprot.org/citations/15842357http://purl.uniprot.org/core/name"J Thromb Haemost"xsd:string
http://purl.uniprot.org/citations/15842357http://purl.uniprot.org/core/pages"724-732"xsd:string
http://purl.uniprot.org/citations/15842357http://purl.uniprot.org/core/title"Liver histology of an afibrinogenemic patient with the Bbeta-L353R mutation showing no evidence of hepatic endoplasmic reticulum storage disease (ERSD); comparative study in COS-1 cells of the intracellular processing of the Bbeta-L353R fibrinogen vs. the ERSD-associated gamma-G284R mutant."xsd:string
http://purl.uniprot.org/citations/15842357http://purl.uniprot.org/core/volume"3"xsd:string
http://purl.uniprot.org/citations/15842357http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/15842357
http://purl.uniprot.org/citations/15842357http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/15842357
http://purl.uniprot.org/uniprot/#_B4E1D3-mappedCitation-15842357http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15842357
http://purl.uniprot.org/uniprot/#_P02675-mappedCitation-15842357http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15842357
http://purl.uniprot.org/uniprot/#_V9HVY1-mappedCitation-15842357http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15842357
http://purl.uniprot.org/uniprot/P02675http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/15842357
http://purl.uniprot.org/uniprot/V9HVY1http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/15842357
http://purl.uniprot.org/uniprot/B4E1D3http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/15842357
▶