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Test ID: LDLM Familial Hypercholesterolemia, LDLR Large Deletion/Duplication, Molecular Analysis

Reporting Name

LDLR Large Del/Dup

Useful For

Aiding in the diagnosis of familial hypercholesterolemia (FH) in individuals with elevated untreated low-density lipoprotein (LDL) cholesterol

 

Distinguishing the diagnosis of FH from other causes of hyperlipidemia, such as familial defective ApoB-100 and familial combined hyperlipidemia

 

Comprehensive LDL receptor genetic analysis for suspect FH individuals who test negative for an LDLR point variant by sequencing (LDLRS / Familial Hypercholesterolemia, LDLR Full Gene Sequencing)

Specimen Type

Whole Blood EDTA


Specimen Required


Multiple cardiovascular-related gene sequencing tests can be performed on a single specimen after a single extraction. See Multiple Cardiovascular-Related Gene Sequencing Tests in Special Instructions for a list of tests that can be ordered together.

 

Container/Tube: Lavender top (EDTA)

Specimen Volume: 3 mL

Collection Instructions: Send specimen in original tube.

Additional Information: Include physician name and phone number with the specimen.


Specimen Minimum Volume

0.5 mL

Specimen Stability Information

Specimen Type Temperature Time
Whole Blood EDTA Ambient (preferred)
  Refrigerated 

Reference Values

An interpretive report will be provided.

Day(s) and Time(s) Performed

Varies

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

81405-LDLR (low density lipoprotein receptor) (eg, familial hypercholesterolemia), duplication/deletion analysis

LOINC Code Information

Test ID Test Order Name Order LOINC Value
LDLM LDLR Large Del/Dup 69486-9

 

Result ID Test Result Name Result LOINC Value
28486 Interp 69047-9
15598 Comment 48767-8
28487 Reviewed By No LOINC Needed
31629 Result 69486-9

Clinical Information

Familial hypercholesterolemia (FH) is an autosomal dominant disorder that is characterized by high levels of low-density lipoprotein (LDL) cholesterol and associated with premature cardiovascular disease and myocardial infarction. FH is caused by variants in the LDLR gene, which encodes for the LDL receptor. Variants in LDLR impair the ability of the LDL receptor to remove LDL cholesterol from plasma via receptor-mediated endocytosis, leading to elevated levels of plasma LDL cholesterol and subsequent deposition in the skin and tendons (xanthomas) and arteries (atheromas).

 

FH can occur in either the heterozygous or homozygous state, with 1 or 2 variant LDLR alleles, respectively. In general, FH heterozygotes have 2-fold elevations in plasma cholesterol and develop coronary atherosclerosis after the age of 30. Homozygous FH individuals have severe hypercholesterolemia (generally >650 mg/dL) with the presence of cutaneous xanthomas prior to 4 years of age, childhood coronary heart disease, and death from myocardial infarction prior to 20 years of age. Heterozygous FH is prevalent in many different populations, with an approximate average incidence of 1 in 500 individuals, but as high as 1 in 67 to 1 in 100 individuals in some populations in South Africa and 1 in 270 in the French Canadian population. Homozygous FH occurs at a frequency of approximately 1 in 1,000,000.

 

Treatment for FH is aimed at lowering the plasma level of LDL and increasing LDL receptor activity. Identification of LDLR variant(s) in individuals suspected of having FH helps to determine appropriate treatment. FH heterozygotes are often treated with 3-hydroxy-3-methylglutaryl CoA reductase inhibitors (ie, statins), either in monotherapy or in combination with other drugs such as nicotinic acid and inhibitors of intestinal cholesterol absorption. Such drugs are generally not effective in FH homozygotes, and treatment in this population may consist of LDL apheresis, portacaval anastomosis, and liver transplantation.

 

The LDLR gene maps to chromosome 19p13 and consists of 18 exons spanning 45 kb. Hundreds of variants have been identified in the LDLR gene, the majority of them occurring in the ligand binding and epidermal growth factor (EGF) precursor homology regions in the 5' region of the gene (type II and III variants, respectively). Although most FH-causing variants are small (eg, point variants), approximately 10% to15% of variants in the LDLR gene are large rearrangements such as exonic deletions and duplications, which are not amenable to sequencing (eg, LDLRS / Familial Hypercholesterolemia, LDLR Full Gene Sequencing) but can be detected by this MLPA assay.

Interpretation

An interpretive report will be provided.

Clinical Reference

1. Hobbs H, Brown MS, Goldstein JL: Molecular genetics of the LDL receptor gene in familial hypercholesterolemia. Hum Mutat 1992:1:445-466

2. Goldstein JL, Hobbs H, Brown MS: Familial hypercholesterolemia. In The Metabolic Basis of Inherited Disease. Edited by CR Scriver, AL Beaudet, D Valle, et al New York, McGraw-Hill Book Company, 2006 pp 2863-2913

3. Van Aalst-Cohen ES, Jansen AC, Tanck MW, et al: Diagnosing familial hypercholesterolemia: the relevance of genetic testing. Eur Heart J 2006;27:2240-2246

4. Soutar AK, Naoumova RP: Mechanisms of disease: genetic causes of familial hypercholesterolemia. Nat Clin Pract Cardiovasc Med 2007;4(4):214-225

5. Schouten JP, McElgunn CJ, Waaijer R, et al: Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res 2002;30(12):e57

Analytic Time

5 days

Method Name

Dosage Analysis by Multiplex Ligation-Dependent Probe Amplification (MLPA)

Testing Algorithm

See Familial/Autosomal Dominant Hypercholesterolemia Diagnostic Algorithm in Special Instructions. 

Forms

1. Familial/Autosomal Dominant Hypercholesterolemia Patient Information (T637) is required in Special Instructions

2. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (T576) is available in Special Instructions.

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

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