Mayo Test Catalog, (Sorted By Test Name) - Mayo Medical ...

LDLM
89073
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). The
majority of LDLR mutations are missense, small insertion, deletion, and other point mutations, most of
which are detected by full-gene sequencing. Approximately 10% to 15% of LDLR mutations are large
rearrangements, such as exonic deletions and duplications, which cannot be detected by full-gene
sequencing.
Useful For: Genetic testing of individuals at risk for known LDLR familial mutation(s)
Interpretation: An interpretive report will be provided.
Reference Values:
An interpretive report will be provided.
Clinical References: 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, WS Sly. New York, McGraw-Hill Book Company, 2006, pp 2863-2913 3. van
Aalst-Cohen ES, Jansen AC, Tanck MW, et al: Diagnosing familial hypercholesterolaemia: the relevance
of genetic testing. Eur Heart J 2006;27:2440-2446
Familial Hypercholesterolemia, LDLR Large
Deletion/Duplication, Molecular Analysis
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 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.
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 mutation by sequencing (LDLRS/81013 Familial Hypercholesterolemia, LDLR Full Gene
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