Scientists discover new genetic defects responsible for familial hypercholesterolemia

Researchers at the Research Laboratory of Lipid Metabolism Disorders and Atherosclerosis of the WCRC for Personalized Medicine found new variants of genetic defects linked to the development of familial hypercholesterolemia.

Familial hypercholesterolemia (FHC) is the most common primary dyslipidemia that causes premature cardiovascular changes. Despite advances in genetic testing and new treatment technologies, detection rates and the level of adequate management of patients with FH remain low. Major scientific challenges are a significant discrepancy between the clinical and genetic diagnosis of the disease and the need for a more accurate CVD risk assessment.

Along with positive and negative results of genetic testing, sometimes gene testing reports describe a variant as having unknown significance, also known as VUS. This means that there is a mutation, but it is not entirely clear how it affects the risks of developing the disease. The study of such variants allows, if detected in a certain number of patients, transferring them to the positive status.

As part of the ongoing WCRC project on familial hypercholesterolemia, 7 new VUS were discovered in the key genes responsible for the development of FH – LDLR, ApoB and LDLRAP1, which have not been previously described, but all of the presented patients having a classic FH phenotype. To exclude the influence on this phenotype of other factors that could lead to a similar clinical picture, an additional testing was carried out (taking into account the polygenic risks of the disease and assessing the lipoprotein (a) level.

Of particular interest is a VUS found in a 29- and 32-year-old brother and sister. Already at clinical examination, they were assigned to a group of very high cardiovascular risk due to high levels of LDL-C, personal and family history of premature CVD and a high coronary artery calcium (Fig. 1).

Scientists at the Research Laboratory of Lipid Metabolism Disorders and Atherosclerosis continue to further study the discovered variants in order to develop changes in the management strategy for this group of patients.

02.12.2022