Sitosterolemia via the ABCG5 Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
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Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
2035 ABCG5$870.00 81479 Add to Order
Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity

To date, only about 100 cases of sitosterolemia have been reported (Escolá-Gil et al. 2014). In a series of 25 unrelated families with a diagnosis of sitosterolemia based on elevated plasma sitosterol levels, pathogenic variants in the ABCG5 and ABCG8 genes were found in 9 of 25 and 16 of 25 families respectively (Lu et al. 2001). Analytical sensitivity for detection of pathogenic variants in the ABCG5 and ABCG8 genes is >95%. Two cases of a deletion of exon 3 in the ABCG5 gene have been reported that are not predicted to be detected by sequencing (Lu et al. 2001).

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Clinical Features

Sitosterolemia is a disorder hallmarked by a 30-100 fold increase in plasma plant sterols. Heightened levels are due to defects in the adenosine triphosphate-binding cassette transporter protein which effluxes free sterols from hepatocytes and enterocytes into the gut lumen. The primary clinical features of sitosterolemia patients are tendon or tuberous xanthomas and accelerated atherosclerosis which have been reported in individuals as young as 4 years of age (Mymin et al. 2003). Hemolytic anemia, stomatocyte formation, and macrothrombocytopenia are common hematologic findings and may be the only clinically observed symptoms in patients (Wang et al. 2014; Escolá-Gil et al. 2014). Clinical colormetric enzyme assays to quantify sterols cannot discriminate between cholesterol and plant sterols making diagnosis difficult (Kidambi and Patel 2008). Genetic testing is helpful in the differential diagnosis of sitosterolemia from cerebrotendinous xanthomatosis, cardiovascular disease, and familial hypercholesterolemia. Ezetimibe, an inhibitor of intestinal cholesterol absorption, has been shown to be effective in reducing plasma sterol levels (Othman et al. 2015).


Sitosterolemia is inherited in an autosomal recessive manner with pathogenic variants in the ABCG5 and ABCG8 genes being responsible for 1/3 and 2/3 of cases respectively (Lee et al 2001; Escolá-Gil et al. 2014; Hubacek et al. 2001). The ABCG5 and ABCG8 genes encode the heterodimer adenosine triphosphate-binding cassette transporter protein present on enterocytes and hepatocytes. In enterocytes, the transporter is located on the apical membrane and promotes efflux of plant sterols back into the intestinal lumen. In the liver, the transporter is responsible for excretion of plant sterols into the bile (Lee et al. 2001). Pathogenic variants in the ABCG5 and ABCG8 genes impair transporter function or surface expression and result in elevated plasma plant sterol levels.

Loss of function pathogenic variants are most commonly found in the ABCG5 gene and include nonsense, frameshift, splice site alterations and gross deletions of exon 3.  Missense variants, primarily occurring in exon 9, have also been reported to be causative for sitosterolemia (Lee et al. 2001; Escolá-Gil et al. 2014; Lu et al. 2001). ABCG5 pathogenic variants are more commonly found in patients of Chinese, Japanese, or Indian decent (Kidambi and Patel 2008).

Testing Strategy

This test involves bidirectional sequencing using genomic DNA of all coding exons of the ABCG5 gene plus ~20 bp of flanking non-coding DNA on each side. We will also sequence any single exon (Test #100) or pair of exons (Test #200) in family members of patients with known mutations or to confirm research results.

Indications for Test

Candidates for testing include patients presenting with xanthomas, premature atherosclerosis, hemolytic anemia, and macrothrombocytopenia. Presence of stomatocytes in bloods smears and elevated plant sterol levels (>20-30mg/dl) are common laboratory findings. Gas chromatography or high performance liquid chromatography are necessary to specifically measure plant sterol levels as colormetric assays to measure sterols do not differentiate between cholesterol and plant sterols (Kidambi and Patel 2008; Lu et al. 2001). 


Official Gene Symbol OMIM ID
ABCG5 605459
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Sitosterolemia AR 210250

Related Tests

CerebroTendinous Xanthomatosis (CTX) via the CYP27A1 Gene
Sitosterolemia Sequencing Panel
Sitosterolemia via the ABCG8 Gene


Genetic Counselors
  • Escolà-Gil J.C. et al. 2014. Current Atherosclerosis Reports. 16: 424. PubMed ID: 24821603
  • Hubacek J.A. et al. 2001. Human Mutation. 18: 359-60. PubMed ID: 11668628
  • Kidambi S., Patel S.B. 2008. Journal of Clinical Pathology. 61: 588-94. PubMed ID: 18441155
  • Lee M.H. et al. 2001. Nature Genetics. 27: 79-83. PubMed ID: 11138003
  • Lu K. et al. 2001. American Journal of Human Genetics. 69: 278-90. PubMed ID: 11452359
  • Mymin D. et al. 2003. Circulation. 107: 791. PubMed ID: 12578886
  • Othman R.A. et al. 2015. The Journal of Pediatrics. 166: 125-31. PubMed ID: 25444527
  • Wang Z. et al. 2014. American Journal of Hematology. 89: 320-4.  PubMed ID: 24166850
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Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 20 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of March 2016, we compared 17.37 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 12 years of our lab operation we have Sanger sequenced roughly 8,800 PCR amplicons. Only one error has been identified, and this was due to sequence analysis error.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 20 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

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Ordering Options

myPrevent - Online Ordering
  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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