A form of Type 2 Hyperlipoproteinemia

Familial Hypercholesterolemia has an autosomal dominant pattern of inheritance.

Characterized by mutations due on the gene encoding the LDL receptor (LDLR gene)

Results in eleveated levels of plasma cholesterol carried by LDL

Symptoms of Familial Hypercholesterolemia include atheromas and xanthomas.

Atheromas are deposits of cholesterol in the coronary artery

Xanthomas are deposits of cholesterol in skin and tendons.

The LDL receptor has 839 amino acids plus a 21 amino acid signal sequence.

The LDL receptor mediates the uptake of exogenous cholesterol bound to LDL

Has apoprotein B-100

LDL receptors are marked by clathrin and binds to LDL which will start receptor mediated endocytosis.

Increase in intracellular cholesterol inhibits HMG CoA reductase

Increase in cholesterol reduces receptor synthesis

Receptor has five distinct structural domains.

The LDLR gene is 45kB long. Has 18 exons.

The receptor has five functional domains.

The ligand-binding domain (5 exons) at the N-terminal end consists of 7 repeated units of 40 amino acids, each of which contains 6 cysteines.

The final domain is coded by exons 17 and 18 and constitutes the cytoplasmic portion of the protein.

LDL receptor mutation (apoB-100)

Autosomal dominant

endocytosis of LDL inhibited

Increased LDL levels, leading to atheromas (arteries) and xanthomas (skin)