Familial Hypercholesterolemia in a Large Kindred

The traditional view that familial hypercholesterolemia (type II hyperlipoproteinemia) is inherited as an autosomal-dominant trait has been recently questioned. Instead, it has been suggested that multiple genes (polygenic inheritance) rather than a single gene (monogenic) might be involved. Investigation of a large Aleutian kindred consisting of 92 members provides evidence that at least one type of familial hypercholesterolemia is determined by a monogenic mechanism. Bimodality in the distribution of total plasma cholesterol values was demonstrated for both near and distant relatives at all ages. The mutant gene in this kindred 1 segregates as an autosomal-dominant trait, 2 specifies elevations in cholesterol of plasma low-density lipoprotein, 3 does not affect the level of plasma triglyceride, and 4 leads to early appearance of xanthomas and coronary atherosclerosis.