Phenotypic heterogeneity of sitosterolemia.

Abstract

Sitosterolemia is a rare autosomal recessive disorder of lipoprotein metabolism characterized by xanthomas and increased plasma concentrations of plant sterols, such as sitosterol. Causative mutations occur in either the ABCG5 or ABCG8 gene, each of which encodes a sterol half-transporter expressed in the intestine. We report five Canadian subjects with nonsense mutations in these half-transporters: four related Caucasian subjects were homozygous for the ABCG8 S107X mutation, and one unrelated Japanese-Canadian subject was homozygous for a complex insertion/deletion (I/D) mutation in ABCG5 exon 3. A female subject with each mutation was symptomatic with coronary atherosclerosis: a 5-year-old ABCG8 S107X homozygote and a 75-year-old ABCG5 exon 3 I/D homozygote; these represent the extreme ends of the spectrum of vascular involvement in sitosterolemia. The largest reductions in plasma concentrations of sitosterol and LDL-cholesterol were seen with ezetimibe or bile acid sequestrant treatment, and less dramatic reductions were seen with statin drug treatment. These findings extend the range of clinical phenotypes in sitosterolemia caused by nonsense mutations in either ABCG5 or ABCG8.

• Authors: Jian Wang, Tisha Joy, David Mymin, Jiri Frohlich, Robert A Hegele
• Journal: Journal of lipid research (J Lipid Res) Vol. 45 Issue 12 Pg. 2361-7 (Dec 2004) ISSN: 0022-2275 [Print] United States
• PMID: 15375183 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ABCG5 protein, human
• ABCG8 protein, human
• ATP Binding Cassette Transporter, Subfamily G, Member 5
• ATP Binding Cassette Transporter, Subfamily G, Member 8
• ATP-Binding Cassette Transporters
• Lipoproteins
• Sitosterols

Topics

• ATP Binding Cassette Transporter, Subfamily G, Member 5
• ATP Binding Cassette Transporter, Subfamily G, Member 8
• ATP-Binding Cassette Transporters (genetics, metabolism)
• Adult
• Aged
• Aged, 80 and over
• Amino Acid Sequence
• Base Sequence
• Child
• Child, Preschool
• Female
• Humans
• Lipoproteins (genetics, metabolism)
• Male
• Middle Aged
• Molecular Sequence Data
• Pedigree
• Phenotype
• Sitosterols (blood)
• Xanthomatosis (physiopathology)