GeneSeq®: Cardio - Familial Hypercholesterolemia Profile

CPT: 81401; 81406(x2)
Updated on 7/28/2018
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Test Details

Test Includes

This test covers all coding nucleotides of LDLR 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 APOB where all disease associated mutations have been found (within a 200-nucleotide region in exon 26 of APOB).

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.

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 Agilent Sure Select XT® enrichment method and the Illuminar next-generation sequencing platform. Regions of interest include all exons and splice junctions for each gene and limited regions for APOB (556bp of exon 26). 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 ≥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: http://hgvs.org/). Variants known to be benign and synonymous variants not previously recorded in our internal variant data bases are not reported.

Additional Information

Genetic testing for presence of a germline mutation in the genes known to be associated with FH can confirm a diagnosis of FH and also facilitate detection of at-risk children in affected families. Mutations in the genes LDLR, APOB, and PCSK9 account for more than 90% of cases of FH.

Specimen Requirements

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

Clinical Information

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).

References

Gotto AM Jr. Targeting high-risk young patients for statin therapy. JAMA. 2004 Jul 21;292(3):377-378.15265854
Leren TP. Cascade genetic screening for familial hypercholesterolemia. Clin Genet. 2004 Dec;66(6):483-487.15521974
Lloyd-Jones D, Adams RJ. Brown TM, et al. Heart disease and stroke statistics-2010 update: A report from the American Heart Association. Circulation. 2010 Feb 23;121(7):e46-e215.20019324
Oram JF. Tangier disease and ABCA1. Biochim Biophys Acta. 2000 Dec 15;1529(1-3):321-330.11111099
Rodenburg J, Vissers MN, Wiegman A, et al. Statin treatment in children with familial hypercholesterolemia; the younger, the better. Circulation. 2007 Aug 7;116(6):664-668.17664376
Sanghera DK, Aston CE, Saha N, Kamboh MI. DNA polymorphisms in two paraoxonase genes (PON1 and PON2) are associated with the risk of coronary heart disease. Am J Hum Genet. 1998 Jan;62(1):36-44.9443862
Takada D, Emi M, Ezura Y, et al. Interaction between the LDL-receptor gene bearing a novel mutation and a variant in the apolipoprotein A-II promoter: molecular study in a 1135-member familial hypercholesterolemia kindred. J Hum Genet. 2002;47(12):656-664.12522687
Varret M, Abifadel M, Rabès JP, Boileau C. Genetic heterogeneity of autosomal dominant hypercholesterolemia. Clin Genet. 2008 Jan;73(1):1-13.18028451
Willer CJ, Sanna S, Jackson AU, et al. Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet. 2008 Feb;40(2):161-169.18193043
Wilson P, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation. 1998 May 12;97(18):1837-1847.9603539

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
452040 GeneSeq: Coronary Artery 3Gene 452041 Specimen Type: 31208-2
452040 GeneSeq: Coronary Artery 3Gene 452042 Results: 48003-8
452040 GeneSeq: Coronary Artery 3Gene 452043 Key Findings 53037-8
452040 GeneSeq: Coronary Artery 3Gene 452044 Additional Information 49549-9
452040 GeneSeq: Coronary Artery 3Gene 452045 Gene Information 51968-6
452040 GeneSeq: Coronary Artery 3Gene 452046 Tech Spec Results 51958-7
452040 GeneSeq: Coronary Artery 3Gene 452047 Seq Variants Detected 69548-6
452040 GeneSeq: Coronary Artery 3Gene 452048 Disclaimer 62364-5
452040 GeneSeq: Coronary Artery 3Gene 452049 Director Review: 48672-0
452040 GeneSeq: Coronary Artery 3Gene 452050 PDF 51969-4

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The LOINC® codes are copyright © 1994-2018, Regenstrief Institute, Inc. and the Logical Observation Identifiers Names and Codes (LOINC) Committee. Permission is granted in perpetuity, without payment of license fees or royalties, to use, copy, or distribute the LOINC® codes for any commercial or non-commercial purpose, subject to the terms under the license agreement found at https://loinc.org/license/. Additional information regarding LOINC® codes can be found at LOINC.org, including the LOINC Manual, which can be downloaded at LOINC.org/downloads/files/LOINCManual.pdf