Mutations in PCSK9 cause autosomal dominant hypercholesterolemia

@article{Abifadel2003MutationsIP,
  title={Mutations in PCSK9 cause autosomal dominant hypercholesterolemia},
  author={Marianne Abifadel and Mathilde Varret and Jean-Pierre Rab{\`e}s and Delphine Allard and Khadija Ouguerram and Martine Devillers and Corinne Cruaud and Suzanne Benjannet and Louise Wickham and Dani{\`e}le Erlich and Aur{\'e}lie Derr{\'e} and Ludovic Vill{\'e}ger and Michel Farnier and Isabel Beucler and Eric Bruckert and Jean Chambaz and Bernard Chanu and Jean Michel Lecerf and Gérald Luc and Philippe Moulin and Jean Weissenbach and Annick Prat and Michel Krempf and Claudine Junien and Nabil G. Seidah and Catherine Boileau},
  journal={Nature Genetics},
  year={2003},
  volume={34},
  pages={154-156}
}
Autosomal dominant hypercholesterolemia (ADH; OMIM144400), a risk factor for coronary heart disease, is characterized by an increase in low-density lipoprotein cholesterol levels that is associated with mutations in the genes LDLR (encoding low-density lipoprotein receptor) or APOB (encoding apolipoprotein B). We mapped a third locus associated with ADH, HCHOLA3 at 1p32, and now report two mutations in the gene PCSK9 (encoding proprotein convertase subtilisin/kexin type 9) that cause ADH. PCSK9… 
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The three main genetic defects that lead to FH are defects in the LDL receptor gene, apolipoprotein B-100 (ApoB-100) gene4, and proprotein convertase subtilisin/Kexin type 9 (PCSK9) gene, which account for 60 to 80 percent of patients with definite FH.
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PCSK9 Variants in Familial Hypercholesterolemia: A Comprehensive Synopsis
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A large number of studies have focused on finding effective diagnostic and therapeutic methods based on PCSK9, one of the main pathogenic FH genes, whose contribution to FH deserves more explorative research.
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The results showed that the effect of the S127R mutation of PCSK9 on plasma cholesterol homeostasis is mainly related to an overproduction of apolipoprotein B100.
A new PCSK9 gene promoter variant affects gene expression and causes autosomal dominant hypercholesterolemia.
TLDR
PCSK9 is a rare cause of ADH in Spanish population and, up to what the authors know, none of the previously described mutations has been detected, but a new mutation is identified that could cause ADH by increasing the transcription of PCSK9.
MOLECULAR CHARACTERIZATION AND SPECTRUM OF MUTATIONS ASSOCIATED WITH AUTOSOMAL DOMINANT HYPERCHOLESTEROLEMIA
TLDR
To investigate genotype-phenotype correlations in FH carrying different mutations of the LDL-R gene, the frequency and spectrum of mutations causing FH in patients attending the different Italian lipid clinics was determined.
Mutations in the PCSK9 gene in Norwegian subjects with autosomal dominant hypercholesterolemia
  • TP Leren
  • Biology, Medicine
    Clinical genetics
  • 2004
TLDR
DNA sequencing of the 12 exons of the PCSK9 gene has been performed in 51 Norwegian subjects with a clinical diagnosis of familial hypercholesterolemia and the notion that mutations within this gene cause autosomal dominant hypercholesterololemia is supported.
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