Prevalence and penetrance of pathogenic and likely pathogenic and gene variants linked to familial hypercholesterolemia and increased risk of ischemic heart disease.

Background: Familial hypercholesterolemia (FH) is a prevalent hereditary disorder, with its monogenic form linked to an elevated risk of early-onset ischemic heart disease. Evaluating the prevalence and penetrance of pathogenic and likely pathogenic variants associated with this disorder would provide valuable information supporting routine FH screening of the general population. Such informed screening would facilitate early identification of at-risk individuals, enabling timely intervention and management.

Genetic and Metabolic Factors of Familial Dysbetalipoproteinemia Phenotype: Insights from a Cross-Sectional Study.

Familial dysbetalipoproteinemia (FD) is a prevalent and highly atherogenic hyperlipoproteinemia associated with the ε2/ε2 genotype or rare variants. The contributions of additional genetic and clinical factors to the FD phenotype remain unclear. We investigated these factors in both autosomal recessive and autosomal dominant forms of FD.

A Novel Bradycardia-Associated Variant in as a Candidate Modifier in Type 3 Long QT Syndrome: Case Report and Deep In Silico Analysis.

Genetic testing for long QT syndrome (LQTS) is straightforward in many families; however, in severe and complex cases, a single disease-causing variant may not be enough to explain all clinical features. In such cases, the search for genetic modifiers may be beneficial for precise diagnosis and management. We describe a three-generational family affected with clinically heterogeneous LQTS type 3 and bradycardia in which a novel missense variant p.

[New pathogenic mutation in LMNA gene: Clinical case of familial cardiomyopathy].

We present a clinical case of familial -associated cardiomyopathy, confirmed by whole genome sequencing. The typical for lamin-associated cardiomyopathy indicates pathogenic nature of the mutation in the first exon of gene, previously considered a mutation of unknown clinical significance. The presented clinical case demonstrates a radical change in patient treatment strategies in the context of the widespread introduction of molecular genetic research methods into practice.

On Penetrance Estimation in Family, Clinical, and Population Cohorts.

In recent years, there has been a considerable influx of publications assessing the penetrance of pathogenic variants associated with monogenic diseases with dominant inheritance. As large and diverse groups have been sequenced, it has become clear that incomplete penetrance is common to most hereditary diseases, as numerous molecular, genetic, or environmental factors can cause clinical diversity among the carriers of the same variant. In this review, we discuss some of these factors and focus on the existing approaches to estimating penetrance, depending on the data available and their application to different data sets.