Missense mutation Leu72Pro located on the carboxyl terminal amphipathic helix of apolipoprotein C-II causes familial chylomicronemia syndrome

Clin Chim Acta. 2006 Feb;364(1-2):256-9. doi: 10.1016/j.cca.2005.07.025. Epub 2005 Sep 8.


Background: Chylomicronemia syndrome can be caused by 2 autosomal recessive disorders - lipoprotein lipase (LPL) deficiency and apolipoprotein C-II (apo C-II) deficiency.

Methods: We described 2 siblings with chylomicronemia syndrome of a consanguineous family. To determine the molecular basis of chylomicronemia syndrome in this family, we performed direct DNA sequencing of the LPL and APOC2 genes of the proband.

Results: A novel homozygous mutation, Leu72Pro, in the APOC2 gene was found in both siblings whereas their parents were carriers. No LPL mutations were detected in the siblings. Apo C-II contains 3 amphipathic alpha helices; the C-terminal alpha helix is composed of residues 64 to 74. Substitution of residue 72 from a helix former leucine to a helix breaker, proline, is predicted to change the secondary structure of the C-terminal helix and subsequently alter the interaction between apo C-II and LPL.

Conclusions: To our knowledge, Leu72Pro is the first missense mutation identified in the C-terminal of apo C-II. The result is consistent with the current biochemical and structural findings that the C-terminal helix of apo C-II is important for activation of LPL.

Publication types

  • Case Reports

MeSH terms

  • Apolipoprotein C-II
  • Apolipoproteins C / deficiency
  • Apolipoproteins C / genetics*
  • Base Sequence
  • Child, Preschool
  • Consanguinity
  • DNA Mutational Analysis
  • Female
  • Humans
  • Hyperlipoproteinemia Type I / enzymology
  • Hyperlipoproteinemia Type I / genetics*
  • Infant
  • Lipoprotein Lipase / deficiency
  • Lipoprotein Lipase / genetics*
  • Mutation, Missense*
  • Sequence Homology, Nucleic Acid
  • Siblings
  • Syndrome


  • Apolipoprotein C-II
  • Apolipoproteins C
  • Lipoprotein Lipase

Associated data

  • OMIM/207750
  • OMIM/238600