FHNext

Familial hypercholesterolemia is an inherited disorder characterized by high cholesterol and an increased risk for heart disease. FHNext is a 4-gene panel that analyzes genes associated with familial hypercholesterolemia, clarifying a diagnosis and allow for individualized disease management and treatment.

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Test Code 8680
Turnaround Time (TAT) 14-21 days
Number of Genes 4
Specimen Requirements Click here

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Why Is This Important?

Knowing if your patient has Familial Hypercholesterolemia can help you determine their future coronary artery disease risk and guide your medical management recommendations. Key benefits include:

  1. Confirm a diagnosis, particularly when clinical criteria are unclear or borderline in an individual
  2. Help tailor medical treatment, including avoiding/adjusting simvastatin use based on SLCO1B1 genotype
  3. Clarify risks to family members, including the inheritance pattern

When To Consider Testing

  • For people 20 years of age or older, if LDL Cholesterol is >190 mg/dL or Non-HDL Cholesterol is >220 mg/dL
  • For people under 20 years of age, if LDL Cholesterol is >160 mg/dL or Non-HDL Cholesterol is >190 mg/dL
  • If there is a family history of premature cardiovascular disease or hypercholesterolemia

Mutation Distribution and Detection Rates

~70% of patients with a diagnosis of FH have a mutation in one of the FHNext genes (clinical sensitivity). FHNext can detect >99.9% of described mutations in the included genes, when present (analytic sensitivity).

Test Description

FHNext includes 4 genes associated with FH: APOB, LDLR, PCSK9, and LDLRAP1. Genomic deoxyribonucleic acid (gDNA) is isolated from the patient’s specimen using a standardized kit and quantified. Sequence enrichment of the targeted coding exons and adjacent intronic nucleotides is carried out by a bait-capture methodology using long biotinylated oligonucleotide probes, followed by polymerase chain reaction (PCR) and NGS. Sanger sequencing is performed for any regions missing or with insufficient read depth coverage for reliable heterozygous variant detection. Reportable small insertions and deletions, potentially homozygous variants, variants in regions complicated by pseudogene interference, and single nucleotide variant calls not satisfying 100x depth of coverage and 40% het ratio thresholds are verified by Sanger sequencing.1 This assay targets all coding domains, and well into the flanking 5’ and 3’ ends of all the introns and untranslated regions. Gross deletion/duplication analysis is performed utilizing a targeted chromosomal microarray for APOBLDLR, and PCSK9. Analysis of the pharmacogenetic c.521T>C SNP in the SLCO1B1 gene is performed. If Specific Site Analysis is requested, only specific region(s) of DNA is (are) amplified by PCR and sequenced.

 

1. Mu W, et al. Sanger confirmation is required to achieve optimal sensitivity and specificity in next-generation sequencing panel testing. J Mol Diagn. 2016. 18(6):923-932.

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