Familial hypercholesterolemia has been proposed as a disease to be treated by gene therapy. The molecular basis of familial hypercholesterolemia is which of the following?

a. Absence of hepatic low density lipoprotein receptors

The molecular basis of familial hypercholesterolemia is a mutation in the gene that encodes the low density lipoprotein (LDL) receptor. Patients who inherit one abnormal allele have moderate elevations in plasma LDL and suffer premature coronary heart disease. The prevalence of heterozygotes in most populations is 1 in 500, representing approximately 5% of patients under 45 who suffer myocardial infarction. Patients with two abnormal LDL receptor alleles have severe hypercholesterolemia and life-threatening coronary artery disease. Characterization of mutant alleles has revealed a variety of mutations including deletions, insertions, missense mutations, and nonsense mutations. Class 1 mutations are associated with no detectable protein and are often caused by gene deletions. Class 2 mutations lead to abnormalities in intracellular processing of the protein. Class 3 mutations specifically affect binding of the ligand LDL, and class 4 mutations encode receptor proteins that do not internalize within hepatocytes.