title: Beta-sitosterolaemia: a new nonsense mutation in the ABCG5 gene.
abstract: BACKGROUND
  Sitosterolaemia is a rare autosomal recessive disorder characterised by elevated plasma levels of plant sterols and cholesterol. Sitosterolaemia is caused by gene mutations in either of two ATP-binding cassette (ABC) half transporters, ABCG5 and ABCG8. The plasma sterol profile and genetic analysis of a 10-year-old girl who had tuberous xanthomas is the subject of this report.
  
  
  METHODS
  Genomic DNA was isolated from white blood cells from the proband, her family and a control group of healthy people. All exons of ABCG5 and ABCG8 were sequenced. Plasma cholesterol and triglycerides were measured by routine methods. All other plasma sterols were measured by Gas Chromatography coupled to Mass Spectrometry.
  
  
  RESULTS
  The proband was found to be homozygous for a single nucleotide mutation in exon 10 of the ABCG5 gene, consisting of a C to T transition at nucleotide 1336 of the coding sequence, which results in the premature termination of the ABCG5 protein at amino acid 446 (Arg446X). Her mother and brother were also homozygous for the same mutation and all had elevated plasma beta-sitosterol levels. The father was heterozygous and showed normal beta-sitosterol levels. This mutation was not found in healthy normolipidaemic subjects.
  
  
  CONCLUSIONS
  We describe a novel nonsense mutation in exon 10 of the ABCG5 gene in a 10-year-old girl showing clinical and biochemical features of sitosterolaemia. This family study broadens the spectrum of the ABCG5/ABCG8 mutations causing sitosterolaemia and helps highlight the correlations between such gene mutations, biochemical phenotype and the development of cardiovascular disease.
authors.affiliation: Department of Internal Medicine, University of Tor Vergata, Rome, Italy. liliana.mannucci@ptvonline.it
authors.forename: L
authors.initials: L
authors.lastname: Mannucci
authors.forename: O
authors.initials: O
authors.lastname: Guardamagna
authors.forename: P
authors.initials: P
authors.lastname: Bertucci
authors.forename: L
authors.initials: L
authors.lastname: Pisciotta
authors.forename: L
authors.initials: L
authors.lastname: Liberatoscioli
authors.forename: S
authors.initials: S
authors.lastname: Bertolini
authors.forename: C
authors.initials: C
authors.lastname: Irace
authors.forename: A
authors.initials: A
authors.lastname: Gnasso
authors.forename: G
authors.initials: G
authors.lastname: Federici
authors.forename: C
authors.initials: C
authors.lastname: Cortese
mesh_terms: D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D002648:Child; D002784:Cholesterol / Q000097:blood; D005091:Exons / Q000235:genetics*; D005190:Family; D005260:Female; D006801:Humans; D007492:Iran / Q000208:ethnology; D008074:Lipoproteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012855:Sitosterols / Q000097:blood; D013261:Sterols / Q000097:blood; D014280:Triglycerides / Q000097:blood; D014973:Xanthomatosis / Q000209:etiology
chemical_list: C416945:ABCG5 protein, human; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D018528:ATP-Binding Cassette Transporters; D008074:Lipoproteins; D012855:Sitosterols; D013261:Sterols; D014280:Triglycerides; C025473:gamma-sitosterol; D002784:Cholesterol