The Present and the Future of Genetic Testing in Familial Hypercholesterolemia: Opportunities and Caveats

We summarize recent advances in the understanding of genetic testing in familial hypercholesterolemia (FH), the use of expanded FH next-generation sequencing panels, and directions for future research.

The uptake of massively parallel sequencing in research and diagnostic laboratories has enabled expanded testing for FH and its phenocopies, with the added advantage that copy number variants can be detected. However, increasing the number of genes tested increases the number of variants detected, which may or may not be pathogenic. Guidelines for assessing variant pathogenicity will assist the provision of accurate and consistent interpretations between centers. Expanded FH panels can identify mutations in other relevant genes, such as APOE, LIPA, and ABCG5/8 and enable the identification of polygenic hypercholesterolemia using LDL genetic risk scores. Increased awareness and understanding of genomics by the public, patients, and health professionals is critical for effectively translating into practice new advances in genetic testing for FH.