Functional characterization of 16 variants found in the LDL receptor gene

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209775%3A_____%2F25%3AN0000006" target="_blank" >RIV/00209775:_____/25:N0000006 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14110/25:00142560 RIV/65269705:_____/25:00082397
Result on the web
<a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC12454892/" target="_blank" >https://pmc.ncbi.nlm.nih.gov/articles/PMC12454892/</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.jlr.2025.100873" target="_blank" >10.1016/j.jlr.2025.100873</a>

Result language
angličtina
Original language name
Functional characterization of 16 variants found in the LDL receptor gene
Original language description
Familial hypercholesterolemia (FH) is a disorder of cholesterol metabolism characterized by elevated LDL-cholesterol levels. The most common cause of FH is pathogenic variants in the LDL receptor (LDLR) gene. To shed light on the functional impact of selected LDLR variants, we functionally characterized 16 LDLR genetic variants alongside 10 control variants. We performed in vitro assays based on transient expression of WT and mutant LDLRs in LDLR-deficient Chinese hamster ovary cells. We used flow cytometry to analyze the relative amount of LDLRs expressed on the cell surface and the relative amount of internalized LDL. In addition, we analyzed the expression and maturation of LDLR protein by Western blotting. Of the 16 studied variants, two variants (p.(Asn272Thr) and p.(Arg574Leu)) did not exhibit a defect in LDLR function, one variant (p.(Ala540Thr)) exhibited a defect in LDL binding and/or internalization despite normal LDLR cell surface expression, and the remaining 13 variants had a detrimental effect on both LDLR cell surface expression and LDL internalization. The information presented in this study contributes to the clinical classification of LDLR variants and a more precise diagnosis of FH patients, highlighting the type of defect each variant produces.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30201 - Cardiac and Cardiovascular systems

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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