2.1. Familial Hypercholesterolemia

Mutations in the LDLR gene cause a form of high cholesterol called familial hypercholesterolemia. More than 2,000 mutations have been identified in this gene. Some of these genetic changes reduce the number of low-density lipoprotein receptors produced within cells. Other mutations disrupt the receptor's ability to remove LDLs from the blood. As a result, people with mutations in the LDLR gene have very high blood cholesterol levels. As the excess cholesterol circulates through the bloodstream, it is deposited abnormally in tissues such as the skin, tendons, and arteries that supply blood to the heart (coronary arteries). A buildup of cholesterol in the walls of coronary arteries greatly increases a person's risk of having a heart attack.

Most people with familial hypercholesterolemia inherit one altered copy of the LDLR gene from an affected parent and one normal copy of the gene from the other parent. These cases are associated with an increased risk of early heart disease, typically beginning in a person's forties or fifties. Rarely, a person with familial hypercholesterolemia is born with two mutated copies of the LDLR gene. This situation occurs when the person has two affected parents, each of whom passes on one altered copy of the gene. The presence of two LDLR gene mutations results in a more severe form of hypercholesterolemia that usually appears in childhood.