Familial Hypercholesterolemia: LDLR Deletion/Duplication MLPA

Clinical Information

Familial hypercholesterolemia has an estimated prevalence of 1 in 200-250 individuals, and copy number variants in LDLR account for up to 10% of cases. This condition is associated with significant elevations in low-density lipoprotein (LDL) cholesterol. In addition, total cholesterol is typically increased (usually greater than 300 mg/dL in untreated individuals) with normal to slight elevations in triglycerides. Familial hypercholesterolemia is associated with increased risk of premature cardiovascular disease, specifically atherosclerosis, and symptoms include angina, heart attack, and rarely stroke. Other findings include a hazy ring along the outer rim of the iris known as corneal arcus and xanthomas, particularly of the hands and Achilles tendon.

Technical Information

• This test is performed using Multiplex Ligation-dependent Probe Amplification (MLPA).
• MLPA analysis is performed to determine if deletions or duplications involving the LDLR gene are present. MLPA is a molecular technique that allows the determination of dosage for specific sequences of interest (Schouten et al. (2002) Nucleic Acids Research 30, e57).
• Probes for all eighteen LDLR coding exons and promoter, in combination with a variety of control probes, are analyzed and quantified.

Specimen Requirements

• The preferred sample type is 3-4 ml of peripheral blood collected in an EDTA (purple top) tube. Extracted DNA and saliva are also accepted for this test. Blood and saliva kits are available by request.
• Send approximately 5µg of extracted DNA at a requested concentration of 90-130 ng/µl. Bead-based extraction is strongly discouraged for MLPA.
• Saliva samples must be submitted in an approved saliva kit.

Transport Instructions

• The blood specimen should be kept at room temperature and delivered via overnight shipping. If shipment is delayed by one or two days, the specimen should be refrigerated and shipped at room temperature. Do not freeze the specimen. Samples collected on Friday can be safely designated for Monday delivery.
• Extracted DNA should be sent at room temperature via overnight delivery.
• Saliva is stable at room temperature and can be delivered via overnight or ground shipping.