Beta-sitosterolaemia: a new nonsense mutation in the ABCG5 gene.
2007
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.
MATERIALS AND 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.
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