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Predictive Modeling and Structure Analysis of Genetic Variants in Familial Hypercholesterolemia: Implications for Diagnosis and Protein Interaction Studies. | LitMetric

AI Article Synopsis

Article Abstract

Purpose Of Review: Familial hypercholesterolemia (FH) is a hereditary condition characterized by elevated levels of low-density lipoprotein cholesterol (LDL-C), which increases the risk of cardiovascular disease if left untreated. This review aims to discuss the role of bioinformatics tools in evaluating the pathogenicity of missense variants associated with FH. Specifically, it highlights the use of predictive models based on protein sequence, structure, evolutionary conservation, and other relevant features in identifying genetic variants within LDLR, APOB, and PCSK9 genes that contribute to FH.

Recent Findings: In recent years, various bioinformatics tools have emerged as valuable resources for analyzing missense variants in FH-related genes. Tools such as REVEL, Varity, and CADD use diverse computational approaches to predict the impact of genetic variants on protein function. These tools consider factors such as sequence conservation, structural alterations, and receptor binding to aid in interpreting the pathogenicity of identified missense variants. While these predictive models offer valuable insights, the accuracy of predictions can vary, especially for proteins with unique characteristics that might not be well represented in the databases used for training. This review emphasizes the significance of utilizing bioinformatics tools for assessing the pathogenicity of FH-associated missense variants. Despite their contributions, a definitive diagnosis of a genetic variant necessitates functional validation through in vitro characterization or cascade screening. This step ensures the precise identification of FH-related variants, leading to more accurate diagnoses. Integrating genetic data with reliable bioinformatics predictions and functional validation can enhance our understanding of the genetic basis of FH, enabling improved diagnosis, risk stratification, and personalized treatment for affected individuals. The comprehensive approach outlined in this review promises to advance the management of this inherited disorder, potentially leading to better health outcomes for those affected by FH.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618353PMC
http://dx.doi.org/10.1007/s11883-023-01154-7DOI Listing

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