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A PCSK9 variant and familial combined hyperlipidaemia

M Abifadel1, L Bernier, G Dubuc

  • 1INSERM U781, Clinique Maurice Lamy, hôpital Necker-Enfants malades, 149, rue de Sèvres, 75743 Paris Cedex 15, France. marianne.abi-fadel@inserm.fr

Journal of Medical Genetics
|August 19, 2008
PubMed

Insights

A novel PCSK9 gene mutation, p.L21tri, is linked to familial combined hyperlipidaemia (FCHL). This finding suggests PCSK9 variants play a role in FCHL, impacting cholesterol levels.

Area of Science:

  • Genetics
  • Molecular Biology
  • Cardiovascular Disease

Background:

  • The discovery of PCSK9 gene mutations in 2003 identified a key regulator of low-density lipoprotein cholesterol (LDL-C).
  • Gain-of-function PCSK9 mutations elevate LDL-C by reducing LDL receptors, while loss-of-function variants decrease LDL-C and heart disease risk.

Purpose of the Study:

  • To investigate the role of PCSK9 variants in familial combined hyperlipidaemia (FCHL).
  • To identify novel mutations in the PCSK9 gene associated with dyslipidaemia.

Main Methods:

  • Screening of 25 families with FCHL for PCSK9 gene mutations.
  • Genotyping and analysis of lipid profiles in affected individuals.

Main Results:

  • An insertion mutation (p.L21tri or p.L15_L16ins2L) was identified in the PCSK9 signal peptide in two FCHL families.
  • This mutation was associated with elevated total cholesterol and LDL-C levels.
  • The p.L21tri mutation was also found in a patient with familial hypercholesterolaemia and her father.

Conclusions:

  • PCSK9 variants, including the novel p.L21tri mutation, may contribute to the FCHL phenotype.
  • These findings highlight the importance of considering PCSK9 in the genetic basis of complex lipid disorders like FCHL.
Abstract

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