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

Area of Science:

• Genetics
• Cardiovascular Medicine
• Metabolic Disorders

Background:

• Familial hypercholesterolemia (FH) is a genetic disorder characterized by high LDL cholesterol levels.
• Genetic testing is crucial for diagnosing FH and identifying affected family members.
• Expanded genetic testing may offer additional diagnostic yield in specific cases.

Purpose of the Study:

• To evaluate the diagnostic yield of expanded genetic testing for pathogenic variants in ABCG5, ABCG8, LIPA, and APOE.
• To assess the utility of this testing in individuals with a clinical suspicion of familial hypercholesterolemia.

Main Methods:

• Retrospective review of patients from an Advanced Lipid Disorders Clinic (2015-2023).
• Analysis of genetic testing results for familial hypercholesterolemia, including expanded panels for sitosterolemia, APOE, and LIPA.
• Calculation of the yield for pathogenic variants in the tested genes.

Main Results:

• 607 patients underwent FH genetic testing; 263 had expanded testing.
• A low overall yield of 0.7% for pathogenic variants was observed in ABCG5 and APOE.
• Positive results were twice as common as variants of uncertain significance.

Conclusions:

• Expanded genetic testing can identify pathogenic variants in rare instances for FH patients.
• This approach offers a low but valuable likelihood of diagnostic answers with minimal risk of uncertain variants.