Frameshift mutation in the APOA5 gene causing hypertriglyceridemia in a Pakistani family: Management and considerations for cardiovascular risk

J Clin Lipidol. Sep-Oct 2016;10(5):1272-7. doi: 10.1016/j.jacl.2016.07.009. Epub 2016 Aug 9.


We report a novel homozygous apolipoprotein A5 (APOA5) frameshift mutation (c.G425del-C, p.Arg143AlafsTer57) identified in a 12-year-old boy of Pakistani origin with severe hypertriglyceridemia (up to 35 mmol/L) and type V hyperlipoproteinemia. The patient did not respond to fibrate therapy, but his condition improved under a very low fat diet, although compliance was suboptimal. Heterozygous status was detected in both parents (consanguineous union) and one sibling, all showing moderate hypertriglyceridemia (between 5 and 10 mmol/L). There was a significant family history of premature cardiovascular disease. The index case was also diagnosed with a coronary artery anomaly. Considering the recently reported association of rare mutations in APOA5 with the risk of early myocardial infarction, we discuss the implications of these findings for the young man and his family.

Keywords: APOA5; Cardiovascular risk; Genetics; Hypertriglyceridemia; Management.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apolipoprotein A-V / genetics*
  • Asian Continental Ancestry Group / genetics*
  • Bezafibrate / therapeutic use
  • Child
  • DNA Mutational Analysis
  • Frameshift Mutation
  • Humans
  • Hypertriglyceridemia / diagnosis*
  • Hypertriglyceridemia / drug therapy
  • Hypertriglyceridemia / genetics
  • Male
  • Pakistan
  • Pedigree


  • APOA5 protein, human
  • Apolipoprotein A-V
  • Bezafibrate