Back to Search
Start Over
Phenotypic heterogeneity of sitosterolemia.
- Source :
-
Journal of lipid research [J Lipid Res] 2004 Dec; Vol. 45 (12), pp. 2361-7. Date of Electronic Publication: 2004 Sep 16. - Publication Year :
- 2004
-
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.
- Subjects :
- ATP Binding Cassette Transporter, Subfamily G, Member 5
ATP Binding Cassette Transporter, Subfamily G, Member 8
ATP-Binding Cassette Transporters genetics
ATP-Binding Cassette Transporters metabolism
Adult
Aged
Aged, 80 and over
Amino Acid Sequence
Base Sequence
Child
Child, Preschool
Female
Humans
Lipoproteins genetics
Lipoproteins metabolism
Male
Middle Aged
Molecular Sequence Data
Pedigree
Phenotype
Sitosterols blood
Xanthomatosis physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-2275
- Volume :
- 45
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Journal of lipid research
- Publication Type :
- Academic Journal
- Accession number :
- 15375183
- Full Text :
- https://doi.org/10.1194/jlr.M400310-JLR200