Familial Hypercholesterolaemia

Abstract

Familial hypercholesterolaemia is a genetic disease, resulting from mutation of the low‐density lipoprotein (LDL) receptor, that is characterized clinically by elevation of LDL cholesterol in the blood and premature atherosclerosis.

Keywords: cholesterol; LDL receptor; low‐density lipoprotein; genetic disease; autosomal dominant; tendon xanthoma; receptor‐mediated endocytosis

Figure 1.

Examples of tendon xanthomas seen in patients with familial hypercholesterolaemia. Reprinted with permission from Goldstein JL, Hobbs HH and Brown MS (1995) Familial hypercholesterolaemia. In: Scriver CR, Beaudet AL, Sly WS and Valle D (eds) The Metabolic and Molecular Bases of Inherited Disease, vol. 2, pp. 1981–2030. New York: McGraw‐Hill.

Figure 2.

Uptake of lipoprotein particles by the low‐density lipoprotein receptor. Entry of a receptor–ligand complex into cells occurs at clathrin‐coated pits. The complex is subsequently delivered to the low‐pH environment of the endosome, where dissociation of the complex takes place. The receptor is then returned to the cell surface in a process called receptor recycling. After Brown MS and Goldstein JL (1986) Science232: 34–47.

Figure 3.

The modular domain organization of the low‐density lipoprotein (LDL) receptor. LA, LDL‐A ligand‐binding modules; EG, epidermal growth factor‐like modules; LY, repeats containing a YWTD consensus motif; EGFP, epidermal growth factor precursor. After Springer TA (1998) Journal of Molecular Biology283: 837–862.

Figure 4.

Model illustrating the X‐ray structure of the fifth ligand‐binding module of the low‐density lipoprotein receptor. Side‐chains are superimposed on a ribbon trace of the module backbone. Cysteine and additional residues are labelled as reference points. The bound calcium ion is indicated by a blue sphere. Familial hypercholesterolaemia mutations are located at structurally significant residues. Figure generated using the program Insight II. Reprinted with permission from Fass DF, Blacklow S, Kim PS and Berger JM (1997) Nature388: 691–693.

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Further Reading

Brown MS and Goldstein JL (1986) A receptor‐mediated pathway for cholesterol homeostasis. Science 232: 34–47.

Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (1993) Summary of the Second Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). Journal of the American Medical Association 269: 3015–3023.

Fass DF, Blacklow S, Kim PS and Berger JM (1997) Molecular basis of familial hypercholesterolaemia from structure of LDL receptor module. Nature 388: 691–693.

Goldstein JL, Hobbs HH and Brown MS (1995) Familial hypercholesterolemia. In: Scriver CR, Beaudet AL, Sly WS and Valle D (eds) The Metabolic and Molecular Bases of Inherited Disease, vol. 2, pp. 1981–2030. New York: McGraw‐Hill

LDLR locus website (1996) [www.ucl.ac.uk/fh/]

Rifai N, Bachorik PS and Albers JJ (1999) Lipids, lipoproteins, and apolipoproteins. In: Burtis CA and Ashwood ER (eds) Tietz Textbook of Clinical Chemistry, 3rd edn, pp. 809–861. Philadelphia: WB Saunders.

Witzum JL (1996) Drugs used in the treatment of hyperlipoproteinemias. In: Hardman JG, Gilman AG and Limbird LE (eds) Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th edn, pp. 875–897. New York: McGraw‐Hill.

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How to Cite close
Fisher, Carl, Bernstein, Bradley E, and Blacklow, Stephen C(Apr 2001) Familial Hypercholesterolaemia. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0002011]