Familial hypercholesterolaemia: mutations in the gene for the low-density-lipoprotein receptor

Familial hypercholesterolaemia is a co-dominant inherited disorder of lipoprotein metabolism, in which defects in the gene for the low-density-lipoprotein (LDL) receptor result in a twofold increase in the plasma concentration of cholesterol and moderate-to-severe premature coronary heart disease. Many mutations in the gene for the LDL receptor that have different effects on the structure and function of this multifunctional protein have been found, but it is not yet clear whether the nature of the mutation determines the severity of the disorder. This question is being answered by comparing patients with well-characterized mutations, and recent work suggests that other genetic or environmental factors may be important in modulating the effect of the defect in LDL-receptor function in patients who are heterozygous for the disorder.