A nonsense mutation in the apolipoprotein A-I gene is associated with high-density lipoprotein deficiency and periorbital xanthelasmas.

Conflicting data from epidemiological trials, genetic family studies, transgenic animal models, and in vitro experiments have created controversy regarding the importance of HDL and apolipoprotein (apo) A-I for reverse cholesterol transport and protection from atherosclerosis. In this study we identified a homozygous nonsense mutation in codon 32 (Q32X) of the apoA-I gene as the molecular basis of apoA-I deficiency in a 31-year-old woman who did not present with clinical signs of atherosclerosis. Despite half-normal plasma concentrations of HDL cholesterol and apoA-I in subjects heterozygous for this mutation, the history of the patient's large family did not indicate any increased prevalence of myocardial infarction.