Familial Hypercholesterolemia in a Large Kindred

doi:10.1059/0003-4819-76-5-711

Familial Hypercholesterolemia in a Large Kindred

Evidence for a Monogenic Mechanism

Seattle, Washington, and Anchorage, Alaska

Abstract

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.

Article and Author Information

▸From the Division of Medical Genetics, Department of Medicine, University Hospital, and Division of Metabolism, Department of Medicine, Veterans Administration Hospital; and the Department of Genetics, University of Washington; Seattle, Wash.; and the Alaska Native Medical Center, Anchorage, Alaska.
This work has been supported by USPHS grants GM15253, AM12829, and AM06670. Dr. Schrott and Dr. Goldstein are the recipients of NIH (National Institutes of Health) special Fellowships HE48695 and GM47841-01, respectively. Dr. Hazzard is the recipient of a Clinical Investigatorship of the Veterans Administration.
▸Requests for reprints should be addressed to Arno G. Motulsky, M.D., Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, Wash. 98195.
- Received December 3, 1971.
- Accepted January 28, 1972.