Background:Familial hypolipoproteinemia (FHBL) in an autosomal codominant hypocholesterolemia disorder which prevalence is 1:500/1:3000 in western countries. The clinical phenotype is heterogeneous and homozygous patients presents malabsorption and neurological degeneration, while heterozygous ones show a milder phenotype. A relationship between heterozygous FHBL and liver steatosis has been demonstrated. The basic defect relies on the apolipoprotein B (apoB) gene mutation.Aim of the study consists in correlating an apoB gene mutation with an unexplaind steatohepatitis. Methods:A 63yrs old patient being affected from steatohepatitis since adulthood was investigated for FCHL. Total cholesterol and triglycerides were analyzed by standard kit,apoB by immunoturbidimetric method. Plasma lipoproteins were separeted by ultracentrifugation and apoB analyzed by immunoblotting and elecrophoresed on poliacrylamide gel. The apo B gene mutation detection was performed by PCR amplification of the 5' of the exon 26 and sequenced using the Sequencing System (Promega Co., Madison).Results: The conclusive diagnosis of FHBL was based on the apoB gene mutation detection. This is a two base(AG) deletion at codon 1464 causing a stop codon (TAA) at position 1470. This mutation was detected for the first time in this patient who carries an apoB truncated protein which size correspond to 32,4% of the normal apoB 100. Conclusions: A new truncated protein and gene mutation related to liver steatohepatitis have been detected. Althought a number of apo B gene mutations were previously recognized correlations between apo B and this phenotype is poorly known and possibly misdiagnosed. Furthermore liver steatosis could represent the initial step evolving to steatohepatitis, as the present case demonstrated, to cyrrosis and hepatocarcinoma.

A new mutation of the apolipoprotein B gene originates the apo B32,4 truncated protein.

GUARDAMAGNA, Ornella;BUGIANESI, Elisabetta;BONDONE, claudia;
2002

Abstract

Background:Familial hypolipoproteinemia (FHBL) in an autosomal codominant hypocholesterolemia disorder which prevalence is 1:500/1:3000 in western countries. The clinical phenotype is heterogeneous and homozygous patients presents malabsorption and neurological degeneration, while heterozygous ones show a milder phenotype. A relationship between heterozygous FHBL and liver steatosis has been demonstrated. The basic defect relies on the apolipoprotein B (apoB) gene mutation.Aim of the study consists in correlating an apoB gene mutation with an unexplaind steatohepatitis. Methods:A 63yrs old patient being affected from steatohepatitis since adulthood was investigated for FCHL. Total cholesterol and triglycerides were analyzed by standard kit,apoB by immunoturbidimetric method. Plasma lipoproteins were separeted by ultracentrifugation and apoB analyzed by immunoblotting and elecrophoresed on poliacrylamide gel. The apo B gene mutation detection was performed by PCR amplification of the 5' of the exon 26 and sequenced using the Sequencing System (Promega Co., Madison).Results: The conclusive diagnosis of FHBL was based on the apoB gene mutation detection. This is a two base(AG) deletion at codon 1464 causing a stop codon (TAA) at position 1470. This mutation was detected for the first time in this patient who carries an apoB truncated protein which size correspond to 32,4% of the normal apoB 100. Conclusions: A new truncated protein and gene mutation related to liver steatohepatitis have been detected. Althought a number of apo B gene mutations were previously recognized correlations between apo B and this phenotype is poorly known and possibly misdiagnosed. Furthermore liver steatosis could represent the initial step evolving to steatohepatitis, as the present case demonstrated, to cyrrosis and hepatocarcinoma.
Annual Meeting American Journal Human Genetics
Baltimore,USA
16-19 ottobre 2002
71(4)
427
427
Apolipoprotein B; FHBL; apoB gene; novel truncated apoB; mutation; liver steatosis
Guardamagna O; Bugianesi E; Bonardi R; Molini V; Bondone C; Bobbio A;
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/122135
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