[Familial hypercholesterolemia due to a new mutation in the low density lipoprotein receptor gene]

Area of Science:

• Genetics
• Cardiovascular Medicine
• Biochemistry

Background:

• Familial hypercholesterolemia (FHC) is a significant genetic disorder characterized by elevated serum cholesterol levels.
• This condition is a primary driver for the development of cardiovascular diseases.
• Understanding the genetic underpinnings of FHC is crucial for effective management and prevention strategies.

Purpose of the Study:

• To investigate the specific genetic mutations associated with Familial hypercholesterolemia (FHC) within the Kareliya region.
• To identify novel genetic variations and characterize their prevalence in the studied population.
• To correlate genotypic findings with phenotypic manifestations in FHC patients.

Main Methods:

• Genetic examination of 109 patients diagnosed with FHC, based on Simon Broom criteria.
• Sequencing of the low-density lipoprotein receptor (LDLR) gene and screening for mutations in APOB and PCSK9 genes.
• Comprehensive clinical assessment including lipid profile, glucose levels, ECG, echocardiography, and vascular imaging.

Main Results:

• Confirmed "definitive" FHC in 69.4% and "probable" FHC in 30.6% of patients.
• Identified 13 distinct mutations within the LDLR gene among 109 patients, with seven mutations being reported for the first time globally.
• No major mutations were detected in the APOB and PCSK9 genes. A novel mutation, c.2191delG (p.(Val731Serfs*6)), was characterized and linked to familial dyslipidemia.

Conclusions:

• The genetic landscape of FHC in Kareliya is characterized by several LDLR gene mutations, including novel variants.
• The identified mutations contribute to familial dyslipidemia, highlighting the importance of genetic screening.
• Further research is warranted to fully elucidate the phenotypic expression of atherosclerosis in FHC patients with identified gene mutations.