Genetic testing in dyslipidaemia: An approach based on clinical experience

We have used DNA sequencing in our lipid clinic for >20 years. Dyslipidaemia is typically ascertained biochemically. For moderate deviations in the lipid profile, the etiology is often a combination of a polygenic susceptibility component plus secondary non-genetic factors. For severe dyslipidaemia, a monogenic etiology is more likely, although a discrete single-gene cause is frequently not found. A severe phenotype can also result from strong polygenic predisposition that is aggravated by secondary factors. A young age of onset plus a family history of dyslipidaemia or atherosclerotic cardiovascular disease can suggest a monogenic etiology. With severe dyslipidaemia, clinical examination focuses on detecting manifestations of monogenic syndromic conditions. For all patients with dyslipidaemia, secondary causes must be ruled out. Here we describe an experience-based practical approach to genetic testing of patients with severe deviations of low-density lipoprotein, triglycerides, high-density lipoprotein and also combined hyperlipidaemia and dysbetalipoproteinemia.