• Test Code:
  • Department:
  • Test Synonyms:
    Lipid DisordersFamilial HypercholesterolemiaFHHeterozygous FH (HeFH)Homozygous FH (HoFH)APOBLDLRLDLRAP1PCSK9
  • CPT Code(s):

Familial hypercholesterolemia (FH) is an inherited disorder characterized by severely elevated LDL cholesterol (LDL-C) levels that cause atherosclerotic plaque deposition in arteries. Persons with untreated FH are at an approximately 20-fold increased risk for coronary heart disease (CHD), which may manifest as angina, myocardial infarction, or stroke. Two types of FH can occur: Heterozygous FH (HeFH) and Homozygous FH (HoFH). HeFH results from a single pathogenic variant and is relatively common (prevalence 1:200-500). HoFH results from either two pathogenic variants in a single gene or one pathogenic variant in each of two different genes. HoFH is much rarer with a prevalence of 1:160,000 to 1:1,000,000. Most individuals with HoFH experience severe CHD by their mid-20s and the rate of either death or coronary bypass surgery by the teenage years is high. This next-generation sequencing test is designed to detect mutations in the coding region of 4 genes associated with Hypercholesterolemia.

 Reasons for Referral:

  • Elevated LDL cholesterol.
  • Clinical presentation consistent with hypercholesterolemia including atherosclerotic plaque deposition or CHD.
  • Positive family history for hypercholesterolemia (targeted testing is available if familial mutation is known).
  • Carrier testing.


Next generation sequencing using Illumina NextSeq 500/550 technology of the 4 Hypercholesterolemia-associated genes listed below. Samples are prepared using hybridization probes to enrich exonic regions. This assay does not assess regions of insufficient coverage, introns and promoter regions; pseudogenes; where the reference genome is inaccurate or contains gaps and insertions; and regions of high GC or polynucleotide repeats, but may contain variants that impact gene function.

                 Hypercholesterolemia (4 genes):  APOB, LDLR, LDLRAP1, PCSK9

Specimen Requirements:

Blood: EDTA or ACD (Solution A or B):

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

Saliva: 2 ORAgene™ Saliva Collection Kits (OGR-500) used according to manufacturer instructions.  Please contact KDL Client Services for a Saliva Collection Kit for patients that cannot provide a blood sample.

Assisted Saliva: 4 ORAgene™ Assisted Saliva Collection Kits (OGR-575) used according to manufacturer instructions.  Please contact KDL Client Services for an Assisted Saliva Collection Kit for patients that cannot provide a blood sample.

Skin Fibroblast: Punch Biopsy (Cell cultures will be prepared at KDL and used for testing), or 2 T-25 confluent flasks

DNA: 5-10µg at 60-100ng/uL (DNA must be extracted in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS)

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:

8 weeks

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. GeneReviews:      

          a. Youngblom et al., 2014,http://www.ncbi.nlm.nih.gov/books/NBK174884/

Additional Info:

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