Abstract 18431: Proprotein Convertase Subtilisin Kexin Type 9 Mutations: A Significant Contributor to Familial Hypercholesterolemia in the Western Cape Region of South Africa

Introduction: Familial hypercholesterolemia (FH) is a common genetic disorder characterized by hypercholesterolemia and markedly increased risk of cardiovascular disease. A causal mutation is mostly identified in the low-density-lipoprotein cholesterol receptor (LDLR) gene or in the apolipoprotein B (APOB) gene, while proprotein convertase subtilisin kexin type 9 (PCSK9) gain of function (gof) mutations account for a small minority (<1 %). Genetic work-up in a cohort of FH patients in Cape Town yielded several novel PCSK9 mutations. Hypothesis: The majority of these PCSK9 mutations are gof, to be confirmed by genetic cascade screening. Methods: Individuals referred to the lipid clinic of Groote Schuur Hospital between 1980 and 2016 with clinically diagnosed FH underwent genetic analysis of the LDLR, and if applicable the APOB and PCSK9 genes. Families, in whom a PCSK9 mutation of unknown significance was found, underwent genetic cascade screening as well as laboratory and clinical assessments. Results: A ...