ArticleScientific reports2017
Identification and in vitro characterization of two new PCSK9 Gain of Function variants found in patients with Familial Hypercholesterolemia.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- Functional Analysis of LDLR (Low-Density Lipoprotein Receptor) Variants in Patient Lymphocytes to Assess the Effect of Evinacumab in Homozygous Familial Hypercholesterolemia Patients With a Spectrum of LDLR Activity.Arteriosclerosis, thrombosis, and vascular biology · 2019Trial
- Towards mRNA therapeutics 2.0.Nature reviews. Drug discovery · 2026Review
- The Spectrum of Genetic Causes of Familial Hypercholesterolemia Phenotype.Current atherosclerosis reports · 2026Review
- Cascade screening and genetic variant pathogenicity assessment for familial hypercholesterolemia in a township‑based elderly population.Lipids in health and disease · 2026Article
- Integrated Clinical, Molecular, and Machine Learning Assessment of Familial Hypercholesterolemia.Life (Basel, Switzerland) · 2026Article
- Leveraging human genetic variation to therapeutically target hundreds of genes with dominant & dispensable disease alleles.medRxiv : the preprint server for health sciences · 2026Article
- Current RNA strategies in treating cardiovascular diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Review
- Genetic Heterogeneity of Familial Hypercholesterolemia: Repercussions for Molecular Diagnosis.International journal of molecular sciences · 2023Review
- Genetic and molecular architecture of familial hypercholesterolemia.Journal of internal medicine · 2023Review
- Inclisiran: How Widely and When Should We Use It?Current atherosclerosis reports · 2022Review
- Population-based screening in children for early diagnosis and treatment of familial hypercholesterolemia: design of the VRONI study.European journal of public health · 2022Article
- A Systematic Approach to Assess the Activity and Classification of PCSK9 Variants.International journal of molecular sciences · 2021Article
- Genetic spectrum of familial hypercholesterolemia and correlations with clinical expression: Implications for diagnosis improvement.Clinical genetics · 2021Article
- PCSK9: A Multi-Faceted Protein That Is Involved in Cardiovascular Biology.Biomedicines · 2021Review
- A case of Cerebrotendinous Xanthomatosis with spinal cord involvement and without tendon xanthomas: identification of a new mutation of the CYP27A1 gene.Acta neurologica Belgica · 2021Article
- Lipoprotein metabolism in familial hypercholesterolemia.Journal of lipid research · 2021Review
- A Real-World Experience of Clinical, Biochemical and Genetic Assessment of Patients with Homozygous Familial Hypercholesterolemia.Journal of clinical medicine · 2020Article
- Review
- Molecular mechanisms and genetic regulation in atherosclerosis.International journal of cardiology. Heart & vasculature · 2018Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by pathogenic variants in genes encoding for LDL receptor (LDLR), Apolipoprotein B and Proprotein convertase subtilisin/kexin type 9 (PCSK9). Among PCSK9 variants, only Gain-of- Function (GOF) variants lead to FH. Greater attention should be paid to the classification of variants as pathogenic. Two hundred sixty nine patients with a clinical suspect of FH were screened for variants in LDLR and the patients without pathogenic variants were screened for variants in PCSK9 and APOB. Functional characterization of PCSK9 variants was performed by assessment of protein secretion, of LDLR activity in presence of PCSK9 variant proteins as well as of the LDLR affinity of the PCSK9 variants. Among 81 patients without pathogenic variants in LDLR, 7 PCSK9 heterozygotes were found, 4 of whom were carriers of variants whose role in FH pathogenesis is still unknown. Functional characterization revealed that two variants (p.(Ser636Arg) and p.(Arg357Cys)) were GOF variants. In Conclusions, we demonstrated a GOF effect of 2 PCSK9 variants that can be considered as FH-causative variants. The study highlights the important role played by functional characterization in integrating diagnostic procedures when the pathogenicity of new variants has not been previously demonstrated.
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