Familial hypercholesterolemia: experience from France

Area of Science:

• Genetics
• Cardiovascular Medicine
• Molecular Diagnostics

Background:

• Familial hypercholesterolemia (FH) is a genetic disorder leading to high LDL-cholesterol and premature cardiovascular disease.
• Molecular testing is crucial for diagnosing FH, especially in individuals meeting specific LDL-cholesterol and clinical criteria.

Purpose of the Study:

• To provide an overview of molecular diagnosis for FH in France.
• To describe the mutational spectrum and polygenic susceptibility in FH.
• To identify perspectives for improving FH diagnosis.

Main Methods:

• Analysis of data from the French FH registry, including 3381 index cases.
• Molecular testing for mutations in genes like LDLR, APOB, and PCSK9.
• Gene score calculation to assess polygenic contribution.

Main Results:

• 56% of 2054 tested FH index cases had detectable mutations, primarily in LDLR (93.5%).
• 416 different pathogenic variants were identified in the LDLR gene.
• A polygenic origin was suggested in 36% of patients without identified mutations.

Conclusions:

• The molecular diagnosis of FH in France reveals a diverse mutational landscape.
• Polygenic factors play a significant role in a substantial proportion of FH cases.
• Improving diagnostic efficiency requires enhanced genetic counseling and professional education.