Molecular Genetics Sitosterolemia, ABCG8 Sequencing

Sitosterolemia is an autosomal recessive disorder characterized by high levels of plasma plant sterols (10-25 times higher than those of normal individuals). Additional characteristics of individuals affected with sitosterolemia are tendon and tuberous xanthomas, hemolytic episodes, arthralgias and arthritis, as well as accelerated atherosclerosis and premature coronary artery disease. The high levels of plant sterols in individuals with sitosterolemia are typically caused by increased intestinal absorption and decreased removal of plant sterols. Sitosterolemia is caused by mutations in either of the ATP-binding cassette (ABC) transporters ABCG5 or ABCG8 on chromosome 2p21 which normally function to excretion of sterols. Previously, children affected with sitosterolemia were diagnosed as having “pseudo-homozygous” familial hypercholesterolemia. Current literature indicates that all cases of sitosterolemia are caused by either mutations in ABCG8 (approximately 74% of cases) or ABCG5 (approximately 26% of cases).

Reasons for Referral:

• Identification of inherited genetic defects in ABC transporter(s) in patients with early-onset hypercholesterolemia and high levels of circulating plant sterols.
• Confirmation of a suspected diagnosis with a positive family history of early onset hypercholesterolemia and high levels of circulating plant sterols when a familial mutation is known.
• Predispositional testing for asymptomatic family members with a positive family history of hypercholesterolemia.

For detailed information and ordering instructions, please refer to Full Gene Analysis (1240). Genes may be added or removed from the list below if clinically indicated.

1. Berge K, et al. Accumulation of Dietary Cholesterol in Sitosterolemia Caused by Mutations in Adjacent ABC Transporters. Science 2000; 290: 1771-1775.
2. Lee M, et al. Genetic basis of sitosterolemia. Curr Opin Lipidol 2001; 12(2): 141-149.
3. Lu K, et al. Two Genes that Map to the STSL Locus Cause Sitosterolemia: Genomic Structure and Spectrum of Mutations Involving Sterolin-1 and Sterolin-2 Encoded by ABCG5 and ABCG8, Respectively.  Am. J. Hum. Genet. 2001; 69: 278-290.