Frameshift mutation in the APOA5 gene causing hypertriglyceridemia in a Pakistani family: Management and considerations for cardiovascular risk.
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.
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
Sébastien
S
Thériault
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
Andrew
A
Don-Wauchope
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
Michael
M
Chong
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
Ricky
R
Lali
Department of Pediatrics, McMaster University, Hamilton, ON, Canada.
Katherine M
KM
Morrison
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada. Electronic address: pareg@mcmaster.ca.
Guillaume
G
Paré
D000072040:Apolipoprotein A-V / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D001629:Bezafibrate / Q000627:therapeutic use; D002648:Child; D004252:DNA Mutational Analysis; D016368:Frameshift Mutation; D006801:Humans; D015228:Hypertriglyceridemia / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D008297:Male; D010154:Pakistan; D010375:Pedigree
C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001629:Bezafibrate
APOA5; Cardiovascular risk; Genetics; Hypertriglyceridemia; Management