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Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
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Functional analysis of six uncharacterised mutations in LDLR gene.
Andrea Gomez1, Roberto Colombo2, Alessandro Pontoglio3
1Favaloro University, Lipids and Atherosclerosis Laboratory - IMETTyB - CONICET, Buenos Aires, Argentina; PRICAI-Favaloro Foundation, Buenos Aires, Argentina.
Atherosclerosis
|November 6, 2019
Summary
Six uncharacterized low-density lipoprotein receptor (LDLR) gene variants were functionally assessed for familial hypercholesterolemia (FH). Three variants were classified as pathogenic, one as likely pathogenic, and two as likely benign, aiding in FH diagnosis.
Area of Science:
- Genetics
- Molecular Biology
- Biochemistry
Background:
- Familial hypercholesterolemia (FH) is a genetic disorder affecting lipoprotein metabolism.
- Mutations in the low-density lipoprotein receptor (LDLR) gene are a primary cause of FH.
- Six uncharacterized LDLR variants require functional assessment for clinical relevance.
Purpose of the Study:
- To investigate the functional impact of six uncharacterized LDLR variants.
- To determine the clinical status of these variants in patients with FH.
- To correlate in vitro functional data with clinical and in silico analyses.
Main Methods:
- Site-directed mutagenesis to create specific variants.
- In vitro expression of LDLR protein to assess function.
- Correlation of functional data with clinical information and in silico predictions.
Main Results:
- The six studied variants exhibited varying degrees of impact on LDLR function.
- Functional activity ranged from normal to less than 10% of wild-type.
- Specific variants were classified based on ACMG guidelines: 2 Likely Benign, 3 Pathogenic, 1 Likely Pathogenic.
Conclusions:
- The study provides crucial functional data for six previously uncharacterized LDLR variants.
- Classification of variants aids in the diagnosis and management of familial hypercholesterolemia.
- Functional assessment is essential for defining the pathogenicity of genetic variants.
