Expanded genetic testing in familial hypercholesterolemia-A single center's experience

Am J Prev Cardiol. 2024 May 19:18:100683. doi: 10.1016/j.ajpc.2024.100683. eCollection 2024 Jun.

Abstract

Objective: Assess the yield of genetic testing for pathogenic variants in ABCG5, ABCG8, LIPA, and APOE in individuals with personal and family histories suggestive of familial hypercholesterolemia.

Methods: Retrospective review of patients seen in the Advanced Lipid Disorders Clinic at Johns Hopkins.

Results: In the lipid clinic at a single center during the years 2015-2023, 607 patients underwent genetic testing for familial hypercholesterolemia, of which 263 underwent the expanded genetic testing for sitosterolemia. Eighty-eight patients had genetic testing which included APOE, and 22 patients had testing which included LIPA. Among these, one patient was identified to have a pathogenic variant in APOE and another patient with a pathogenic variant in ABCG5 (0.7 % yield). The frequency of a positive result was double that of a variant of uncertain significance.

Conclusion: These data suggest in rare cases expanded testing can provide answers for patients and families with a minimal likelihood of a variant of uncertain significance.

Keywords: Familial hypercholesterolemia; Genetic testing; Hyperlipidemia.