Molecular Genetics Hypercholesterolemia Panel

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Test Code:

1499
Department:

Molecular Genetics
Test Synonyms:

Lipid Disorders • Familial Hypercholesterolemia • FH • Heterozygous FH (HeFH) • Homozygous FH (HoFH) • APOB • LDLR • LDLRAP1 • PCSK9
CPT Code(s):

81406

Background:

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.

Methodology:

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):

Weekly

Turn Around Time:

8 weeks

Shipment Sensitivity Requirements: