What is the clinical utility of DNA testing in patients with familial hypercholesterolaemia?

Purpose of review Familial hypercholesterolaemia is a common genetic disorder of lipid metabolism in which patients have a significantly elevated risk of early coronary heart disease, which can be substantially lowered by treatment with the statin class of drugs. In many countries in Europe, tracing of relatives using DNA information, once the family mutation has been identified, is being actively carried out. The present review examines the specificity and clinical utility of DNA testing in patients with familial hypercholesterolaemia. Recent findings Technological progress has improved the detection rate in patients with the strongest clinical suspicion of familial hypercholesterolaemia to more than 70-80%. Patients carrying a mutation have, on average, higher LDL cholesterol levels and greater risk of early coronary heart disease, and studies have reported the utility of DNA information in the identification of affected relatives. More than 1000 different molecular causes of familial hypercholesterolaemia are documented in the University College London database, and although more than 90% of these clearly cause familial hypercholesterolaemia, the remainder require careful interpretation. Summary DNA testing, as an adjunct to the measurement of plasma LDL cholesterol levels, has clinical utility in providing an unequivocal diagnosis in patients and in identifying affected relatives at an early age so that they can be offered lifestyle advice and appropriate lipid-lowering therapies, Researchers and DNA diagnostic laboratories need to interpret novel sequence changes with caution in order to avoid a false positive diagnosis.