FH is caused by genetic mutations – either deletions, missense, nonsense, as well as insertion types of mutations – in the gene for the LDL receptor, and the result is a variable loss of function, which can be partial to complete in the ability of the LDL receptor to bind, take up, and clear cholesterol from the LDL particles in the circulation. Patients can be receptor defective, which leads to the expression of LDL receptor isotypes with reduced affinity for LDL on the hepatocyte surface, or receptor negative, in which case they express few to no functional LDL receptors.
J Clin Lipidol. 2011; 5(6).