Familial Hypercholesterolemia (FH) Subpanel (4)

 

Related Genes: APOB, LDLR, LDLRAP1, and PCSK9.

Familial hypercholesterolemia (FH) is characterized by severely elevated plasma levels of low-density lipoprotein (LDL) cholesterol that lead to atherosclerotic plaque deposition in the coronary arteries and proximal aorta at an early age, leading to an increased risk for cardiovascular disease. FH is usually an autosomal dominant disorder with around 75-95% of FH being caused by pathogenic variants in genes encoding the LDL receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9). Autosomal recessive hypercholesterolemia is extremely rare and is caused by pathogenic variants in the low-density lipoprotein (LDL) receptor adaptor protein 1 (LDLRAP1) gene

FH is the most common inherited cardiovascular disease and is estimated to account for up to 3% of myocardial infarctions in individuals under 60. Homozygosity or compound heterozygosity of variants in LDLR, APOB and PCSK9 occurs less frequently and is associated with increased severity and usually severe coronary artery disease in early adulthood. External signs of hypercholesterolemia can also manifest in the form of xanthomata, which can occur around the eyelids and within the tendons of the elbows, hands, knees, and feet. Early diagnosis and treatment can reduce morbidity and mortality.

Clinical Utility: Genetic testing of an individual may be indicated to distinguish hereditary disorder from acquired (non-genetic) causes, provide information on the likelihood of related health issues, guide clinical management, and establish disease risk to other family members and future generations.

Methods: Familial hypercholesterolemia panel offered by Sema4 primarily utilizes next-generation sequencing (NGS) to identify variants within the genes analyzed. Copy number variant (CNV) detection by NGS is also utilized to increase diagnostic yield. Supplemental and confirmatory technology used in this panel may include targeted genotyping, multiplex ligation-dependent probe amplification (MLPA), exon array, quantitative PCR, and Sanger sequencing. Ultra high-resolution medical exon array (UHRMEA) is available for deletion/duplication studies of gene(s) within this panel as either reflex (add-on), concurrent, or standalone test. UHRMEA provides single exon level coverage for the majority of the exons within this panel. Variant classification and interpretation are performed based on the American College of Medical Genetics Standards and guidelines for the interpretation of sequence variants

Targeted Testing: Targeted familial mutation analysis or single gene testing is available for any of the genes on this panel. Prenatal diagnosis is also available for known familial variants; please contact our laboratory at 800-298-6470 to discuss prior to sending any prenatal samples.


Specimen Requirements

 

Postnatal blood samples:
2 yellow-top (ACD-A or ACD-B) or 2 lavender-top (EDTA) tubes, 5-10 mL of blood from the patient are required. One blood tube from both parents is requested.

Newborn/child:
1 yellow-top (ACD-A or ACD-B) or 1 lavender-top (EDTA) tube, 2 mL of blood from the patient are required. Additionally, 1 yellow-top (ACD-A or ACD-B) or 1 lavender-top (EDTA) 5-10 mL tube of blood from both parents is requested.

Prenatal:
Please inquire with lab (800-298-6470 option 2)

Prenatal testing for a known familial variant:

  • Two confluent T-25 flasks of cultured cells from amniotic fluid or chorionic villi
  • >4 mg of direct chorionic villi tissue
  • 15 mL of direct amniotic fluid
  • 5-10 mL of blood in an EDTA tube (lavender top) is required from each biological parent. Parental blood samples may be used for maternal cell contamination studies or confirmation studies.
  • Send in previous report of known familial variant with specimen

 

Extracted DNA

  • A minimum of 10 μL DNA (50-250 ng/μL) is required for testing. 20 μL DNA (50-350 ng/μL) is recommended

 

Saliva

  • Saliva specimens are accepted upon request. Please contact our laboratory to obtain saliva kits
  • Saliva samples should be collected in Oragene DNA (OG-500) kits by DNA Genotek

 

Cheek Swab

  • 1 cheek swab specimen collected from ORAGENE kit from the patient is required. 1 cheek swab specimen collected from ORAGENE kit from both parents is requested.

Ordering Information

 

Shipping:
Samples should be kept and shipped refrigerated or at room temperature. Do not freeze specimens.

Include the following with each sample:

  • Completed and signed test requisition form and informed consent
  • Billing information or payment (include copy of insurance card)
  • Contact information for referring physician
  • Testing to be performed
  • Indication for testing, patient’s family history, ethnic background and prior relevant test results

 

Send same day or overnight (check for morning delivery) to:

Sema4
62 Southfield Ave
Stamford, CT 06902

 

Contact:

gc@sema4.com
Tel: 800-298-6470
Fax: 646-859-6870


Turnaround Time:
Results are reported in 3-4 weeks (for postnatal samples) from the receipt of the specimen.

 

Related Tests:

 

Resources: