Test Details

Use

Confirm a clinical diagnosis of familial hypercholesterolemia (FH) and allow early diagnosis in family members, thus promoting early intervention, which may prevent or repair atherosclerotic damage and lower the risk of coronary artery disease.

Special Instructions

For all tests, specimens must be accompanied by a completed consent form. See sample physician office consent form: Consent for Genetic Testing (in Related Documents). In cases in which a known mutation can be documented, the physician may prefer to order Test 451382, Mutation-specific Sequencing, Whole Blood (link in Related Information). Please call customer service at 866-647-0735 before submitting specimens for family testing (ie, known mutations).

Test Includes

This test covers all coding nucleotides of 3 genes: LDLR, LDLRAP1 and PCSK9, plus at least two and typically 10 flanking intronic nucleotides upstream and downstream of each coding exon, covering the conserved donor and acceptor splice sites, as well as typically 10 flanking nucleotides in the 5' and 3' UTR. This test also covers the region of the APOB where all disease associated mutations have been found (within a 200-nucleotide region in exon 26 of APOB).

Limitations

This analysis does not rule out germline mosaicism, the presence of large chromosomal aberrations (including deletions, insertions, and rearrangements), mutations in regions or genes not included in this test, and possible inter/intragenic interactions between sequence variants. False-positive or false-negative results may occur for reasons that include genetic variants, blood transfusions, bone marrow transplantation, mislabeled specimens, or erroneous representation of family relationships.

This test was developed, and its performance characteristics determined, by LabCorp. It has not been cleared or approved by the US Food and Drug Administration (FDA).

Methodology

Mutation analysis is performed using the AgilentSure Select XT® enrichment method and the Illumina® next-generation sequencing platform. Regions of interest include all exons and splice junctions for each gene and limited regions for the following: APOB (556bp of exon 26) and MED12 (c.3020A>G). Sequencing reads are aligned with the hg19 build of the human genome reference sequence. Analytical sensitivity is based on the depth of coverage across the regions of interest and is provided separately for each gene. Greater than 98% of target bases are synonymous variants not previously recorded at greater than or equal to 20x coverage. Sanger sequencing is used to confirm mutation identity and analyze regions with low coverage. Variants are reported using numbering and nomenclature recommended by the Human Genome Variation Society (HGVS). Variants known to be benign and synonymous variants not previously recorded in our internal variant data bases are not reported.

Specimen Requirements

Information on collection, storage, and volume

Specimen

Whole blood

Volume

10 mL whole blood or 30 mL if ordering multiple tests

Minimum Volume

3 mL

Container

Yellow-top (ACD) tube or Lavender-top (EDTA) tube

Storage Instructions

Maintain specimen at room temperature. Specimen can be stored for brief periods at 4°C.

Causes for Rejection

Frozen specimen; container broken or leaking; container not labeled or label not legible; improper anticoagulant