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Title

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

Authors
Rougemont, A. L.
Male, P. J.
Spahr, Laurent
Published in American Journal of Surgical Pathology. 2006, vol. 30, no. 7, p. 906-911
Abstract 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.
Keywords AdultAfibrinogenemia/ genetics/metabolism/pathologyAmino Acid SequenceAmino Acid SubstitutionArginine/genetics/metabolismEndoplasmic Reticulum/ metabolismFamily HealthFibrinogen/ genetics/metabolismHepatocytes/metabolism/pathologyHumansInclusion Bodies/metabolism/pathologyLiver/metabolism/pathologyLiver Cirrhosis/ genetics/metabolism/pathologyMaleMiddle AgedMolecular Sequence DataMutation, MissensePoint MutationTryptophan/genetics/metabolism
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PMID: 16819336
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RUBBIA-BRANDT, Laura et al. Fibrinogen gamma375 arg-->trp mutation (fibrinogen aguadilla) causes hereditary hypofibrinogenemia, hepatic endoplasmic reticulum storage disease and cirrhosis. In: American Journal of Surgical Pathology, 2006, vol. 30, n° 7, p. 906-911. https://archive-ouverte.unige.ch/unige:9006

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Deposited on : 2010-07-12

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