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Fibrinogen gamma375 arg-->trp mutation (fibrinogen aguadilla) causes hereditary hypofibrinogenemia, hepatic endoplasmic reticulum storage disease and cirrhosis

Publié dansThe American journal of surgical pathology, vol. 30, no. 7, p. 906-911
Date de publication2006
Résumé

Hypofibrinogenemia is a rare inherited disorder characterized by low levels of circulating fibrinogen, caused by mutations within 1 of the 3 fibrinogen genes. We report here the case of a 61-year-old man with chronic liver function test alterations. Liver biopsy examination revealed chronic hepatitis complicated by cirrhosis and weakly eosinophilic globular cytoplasmic inclusions within the hepatocytes, faintly stained with PAS-diastase. On immunohistochemistry, the inclusions reacted strongly with human antifibrinogen antibodies. Coagulation investigations of the propositus and his 2 sons showed low functional and antigenic fibrinogen concentrations that were indicative of hypofibrinogenemia. A liver biopsy performed on the 28-year-old son demonstrated the same globular cytoplasmic inclusions, albeit without associated chronic liver disease. PCR amplification followed by sequencing showed that all 3 were heterozygous for a CGG>TGG mutation at codon 375 of the fibrinogen gamma-chain gene (FGG), corresponding to an Arg>Trp substitution. This is the first in an adult male and the second published case with a discernible hepatic fibrinogen endoplasmic reticulum storage disease due to an FGG Arg375Trp (fibrinogen Aguadilla) mutation. Our results suggest that familial hypofibrinogenemia should be considered in the differential diagnosis of a progressive liver disease associated to hepatocellular intracytoplasmic globular inclusions.

Mots-clés
  • Adult
  • Afibrinogenemia/ genetics/metabolism/pathology
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Arginine/genetics/metabolism
  • Endoplasmic Reticulum/ metabolism
  • Family Health
  • Fibrinogen/ genetics/metabolism
  • Hepatocytes/metabolism/pathology
  • Humans
  • Inclusion Bodies/metabolism/pathology
  • Liver/metabolism/pathology
  • Liver Cirrhosis/ genetics/metabolism/pathology
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation, Missense
  • Point Mutation
  • Tryptophan/genetics/metabolism
Citation (format ISO)
RUBBIA-BRANDT, Laura et al. Fibrinogen gamma375 arg-->trp mutation (fibrinogen aguadilla) causes hereditary hypofibrinogenemia, hepatic endoplasmic reticulum storage disease and cirrhosis. In: The American journal of surgical pathology, 2006, vol. 30, n° 7, p. 906–911. doi: 10.1097/01.pas.0000209848.59670.2c
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Identifiants
ISSN du journal0147-5185
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