A double heterozygote for familial hypercholesterolaemia and familial defective apolipoprotein B-100

Alison Taylor, Graham Bayly, Kunjan Patel, Laura Yarram, Maggie Williams, Julian Hamilton-Shield, Steve E Humphries, Gail Norbury

Research output: Contribution to journalArticle (Academic Journal)peer-review

16 Citations (Scopus)


Autosomal dominant hypercholesterolaemia is genetically heterogeneous, but most commonly (approximately 93%) caused by mutations in low-density lipoprotein receptor (LDLR), where the disease is known as familial hypercholesterolaemia (FH), or apolipoprotein B-100 (APOB) (approximately 5.5%), where the disease is known as familial defective APOB (FDB), while in approximately 2% of patients the mutation is in the proprotein convertase subtilisin/kexin type 9 gene. Homozygous FH having inheritance of two LDLR mutations is a rare but recognized syndrome associated with an extreme hypercholesterolaemia and early-onset coronary artery disease. We present a 15-year-old girl with untreated total cholesterol levels of 8.8 mmol/L who was heterozygous for both the LDLR p.Leu479Pro and APOB p.Arg3527Gln mutation. Cascade testing confirmed the paternal origin of the LDLR mutation and revealed a maternal diagnosis of FDB. This case provides further evidence that the combined effect of an LDLR and an APOB mutation give rise to a phenotype more severe than either mutation alone and is more severe than homozygous FDB, but less severe than homozygous FH. It also highlights the need to consider the presence of additional mutations in families where relatives have varying phenotypes.

Original languageEnglish
Pages (from-to)487-90
Number of pages4
JournalAnnals of Clinical Biochemistry
Issue numberPt 5
Publication statusPublished - Sept 2010


  • Adolescent
  • Aged
  • Apolipoprotein B-100
  • Child
  • Coronary Artery Disease
  • Female
  • Heterozygote
  • Humans
  • Hyperlipoproteinemia Type II
  • Male
  • Middle Aged
  • Pedigree
  • Young Adult


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