Correlation between clinical classification and genetic analysis of familial hypercholesterolemia in premature coronary artery disease in a cohort of Egyptian patients

Area of Science:

• Cardiovascular Genetics
• Medical Diagnostics
• Public Health Genomics

Background:

• Familial Hypercholesterolemia (FH) is a significant risk factor for premature Coronary Artery Disease (CAD).
• Genetic testing is the definitive method for diagnosing FH.
• This study investigated genetically confirmed FH in Egyptian patients with premature CAD.

Purpose of the Study:

• To determine the prevalence of genetically confirmed FH among Egyptian patients presenting with premature CAD.
• To assess the utility of genetic testing in diagnosing FH in this population.

Main Methods:

• Next-generation sequencing (NGS) of 7 key FH-associated genes was performed on 94 premature CAD patients.
• Clinical assessment utilized the Dutch Lipid Network (DLCN) criteria.
• Genetic testing identified pathogenic mutations and variants of uncertain significance.

Main Results:

• Pathogenic mutations were identified in 14 patients, including homozygous FH in 6 individuals.
• Rare variants of uncertain significance were found in 10 patients.
• The overall prevalence of genetically confirmed FH was 14.89%.

Conclusions:

• Genetically confirmed FH affects nearly 15% of premature CAD patients in this Egyptian cohort.
• While the DLCN criteria can aid screening, genetic testing is essential for accurate FH diagnosis.
• High consanguinity rates in Egypt likely contribute to the observed prevalence of both homozygous dominant and recessive FH forms.