Sorted By Test Name - Mayo Medical Laboratories

LDLRK
81183
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; treatment
in these individuals 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). 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: Aiding in the diagnosis of familial hypercholesterolemia (FH) Distinguishing the diagnosis
of FH from other causes of hyperlipidemia, such as familial defective apoB-100 and familial combined
hyperlipidemia
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;1:445-446 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 Gene, Known Mutation
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. LDLR mutations 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 (>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
among many different populations, with an approximate average worldwide incidence of 1 in 500
individuals, but as high as 1 in 67 to 1 in 100 individuals in some South African populations and 1 in 270
in the French Canadian population. Homozygous FH occurs at frequency of approximately 1 in
1,000,000. Treatment is aimed at lowering plasma LDL levels 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-hyroxy-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; treatment
in these individuals 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). 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.
Current as of January 4, 2013 7:15 pm CST 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 713