• Test Code:
  • Department:
  • Test Synonyms:
    ABCG8 full gene sequencingSitosterolemia sequencing
  • CPT Code(s):

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.


Sequencing can be performed by either method below:

Sanger Sequencing: Sequencing of ABCG8 is carried out by amplification of all exons and intron/exon boundaries followed by bi-directional Sanger sequencing. The sensitivity of full gene sequencing is estimated to be approximately 99% for single nucleotide substitutions and small insertions/deletions. All nucleotide changes are analyzed within the context of current databases and literature to predict pathogenicity.

NGS Sequencing: Next generation sequencing will analyze the exons or coding regions of ABCG8 using Illumina NextSeq 500 technology.  Samples are prepared using hybridization probes to enrich exonic regions.  Promoter, intronic, etc. regions are not assessed on our assay, but may contain variants that impact gene function.

Specimen Requirements:

Blood: EDTA or ACD (Solution Aor B):

  • Adult: 5mL
  • Child: 5mL
  • Infant: 2-3mL

Saliva: 2 ORAgene Saliva Kit(s) (OGR-500)

Skin Fibroblast: Punch Biopsy, or 2 T-25 confluent flasks


  • Direct Amniotic Fluid (10-20mL)
  • Direct CVS
  • Cultured Amnio or CVS (2-T25 flasks)

DNA: 1-2µg at a minimum of 50-100ng/µL (DNA must be extracted in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS)

Notice Regarding Molecular Genetic Testing on CVS or Amniotic Fluid Specimens:

  • Maternal cell rule-out testing will be performed on all prenatal specimens received.Please provide maternal blood in addition to the fetal specimen.Additional charges apply for the maternal cell rule-out test.
  • All genetic testing performed on Direct CVS or Direct Amniotic Fluid specimens will be confirmed on cell cultures prepared by Knight Diagnostic Laboratories.Cell cultures will be prepared from the specimen received.Additional charges apply for confirmatory testing.

For routine testing of blood, saliva and buccal swabs, KDL does NOT accept samples from patients within two (2) weeks of a packed cell/platelet transfusion or within four (4) weeks of a whole blood transfusion.  For extraordinary circumstances, where testing must be performed outside of the above windows, please contact our lab.

A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES.  Please include detailed clinical information, including ethnicity, clinical history, and family history.

Test Performed (Days):


Turn Around Time:

14 - 21 days

Shipment Sensitivity Requirements:

  • Package and ship specimen to remain cold, but not frozen. 
  • Ship via overnight express, using the FedEx priority overnight label provided. 
  • Contact Client Services for shipping kits and instructions at (855) 535-1522.


  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.

Additional Info:

The Knight Cancer Institute at Oregon Health & Science University is a pioneer in the field of precision cancer medicine. The institute's director, Brian Druker, M.D., helped prove it was possible to shut down just the cells that enable cancer to grow. This breakthrough has made once-fatal forms of the disease manageable and transformed how cancer is treated. The OHSU Knight Cancer Institute is the only National Cancer Institute-designated Cancer Center between Sacramento and Seattle – an honor earned only by the nation's top cancer centers. It is headquarters for one of the National Cancer Institute's largest research collaboratives, SWOG, in addition to offering the latest treatments and technologies as well as hundreds of research studies and clinical trials.

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