Test ID: LDLM
Familial Hypercholesterolemia, LDLR Large Deletion/Duplication, Molecular Analysis
Secondary ID 
A test code used for billing and in test definitions created prior to November 2011
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Useful For Suggests clinical disorders or settings where the test may be helpful
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 mutation by sequencing (LDLRS/81013 Familial Hypercholesterolemia, LDLR Full Gene Sequencing)
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Method Name A short description of the method used to perform the test
Dosage Analysis by Multiplex Ligation-Dependent Probe Amplification (MLPA)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Aliases Lists additional common names for a test, as an aid in searching
Familial Hypercholesterolemia (FH)
FH
FH (Familial Hypercholesterolemia)
Gene Sequencing
Genotype
Hypercholesterolemia
LDL
LDLR
Low Density Lipoprotein
Sequencing
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
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:
1. Include physician name and phone number with the specimen.
2. Transfusions will interfere with testing for up to 4 to 6 weeks. DNA obtained from white cells may not provide useful information for patients who received a recent transfusion of blood that was not leukocyte-reduced. Wait 4 to 6 weeks until transfused cells have left the patient's circulation before drawing the patient's blood specimen for genotype testing.
Forms:
1. Familial/Autosomal Dominant Hypercholesterolemia Patient Information Sheet (Supply T637) 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 (Supply T576) is available in Special Instructions.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | NA |
| Lipemia | NA |
| Icterus | NA |
| Other | NA |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Whole Blood EDTA | Ambient (preferred) | |
| Refrigerated | ||
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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 mutations in the LDLR gene, which encodes for the LDL receptor. Mutations 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 mutant 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 mutation(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 mutations 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 mutations, respectively). Although most FH-causing mutations are small (eg, point mutations), approximately 10% to15% of mutations in the LDLR gene are large rearrangements such as exonic deletions and duplications, which are not amenable to sequencing (eg, LDLRS/81013 Familial Hypercholesterolemia, LDLR Full Gene Sequencing) but can be detected by this MLPA assay.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Interpretation Provides information to assist in interpretation of the test results
An interpretive report will be provided.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Absence of a mutation does not preclude the diagnosis of familial hypercholesterolemia (FH) unless a specific mutation has already been identified in an affected family member.
In the event of negative results by this technique, LDLR sequencing (LDLRS/81013 Familial Hypercholesterolemia, LDLR Full Gene Sequencing) should be considered to rule out point mutations and small deletions/duplications.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
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
Method Description Describes how the test is performed and provides a method-specific reference
Multiplex ligation-dependent probe amplification (MLPA) is used to detect the presence of large genomic deletions and duplications of all 18 exons and the promoter of LDLR. MLPA requires the hybridization of 2 adjacent probes to each exon; these probes are then amplified by PCR. Deletions are seen as decreased signal relative to control probes arising from the deleted LDLR exon(s), while duplications result in increased signal. (Package insert: SALSA MLPA Kit P062B LDLR, MRC Holland)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Varies
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
81479 -Unlisted molecular pathology procedure
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
| Result ID | Reporting Name | LOINC Code |
|---|---|---|
| 28486 | Interp | 69047-9 |
| 15598 | Comment | In Process |
| 28487 | Reviewed By | N/A |
| 31629 | Result | 69485-1 |
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