Functional Genomics in a cohort of FH mutation negative patients

Background: Clinically, Familial Hypercholesterolaemia (FH) is characterized by high plasma concentrations of total and LDL cholesterol from birth, leading to premature atherosclerosis and coronary heart disease. Currently, the genetic diagnosis is made by finding a functional mutation in one of 3 genes: low-density lipoprotein receptor (LDLR ≈ 90-94%), apolipoprotein B (APOB ≈ 5-9%) and proprotein convertase subtilisin/kexin type 9 (PCSK9 ≈ 1-3%). Problem: Worldwide 50% of clinically diagnosed FH patients lack the identification of a causative mutation to explain their phenotype. Aim: Explore if rare genetic variants in genes involved in monogenic forms of dyslipidaemia can contribute to the FH phenotype.