A novel splicing variant in ABCA1 in the first reported Hong Kong Chinese patient with high-density lipoprotein deficiency

Abstract

Low high-density lipoprotein cholesterol (HDL-C) is a risk factor for cardiovascular disease. Very low HDL-C levels (less than 20 mg/dL), however, were uncommonly seen and can be due to genetic defects involving the metabolic pathway of high-density lipoprotein (HDL). We encountered a 50-year-old Chinese man who was only noticed to have extremely low HDL-C levels after surviving recurrent episodes of myocardial infarction. Further workup revealed the undetectable level of apolipoprotein A-I, the absence of HDL on gel electrophoresis, and a novel heterozygous splicing variant in the ABCA1 gene, which was predicted to be pathogenic by in silico analysis. To the best of our knowledge, this is the first reported Hong Kong Chinese with ABCA1 deficiency and probable Tangier disease. The association of ABCA1 deficiency/Tangier disease and accelerated atherosclerosis is discussed.