The First Japanese Case of Familial Hypercholesterolemia Caused by an apolipoprotein E (APOE) p.Leu167del Mutation

We herein report the first Japanese case of familial hypercholesterolemia (FH) caused by a specific mutation in apolipoprotein E (APOE) [c.500_502delTCC (p.Leu167del)]. The proband was a 38-year-old man diagnosed with FH based on the clinical findings. Genetic testing revealed a rare pathogenic variant in APOE but no relevant mutation in any "FH genes," including low-density lipoprotein (LDL) receptor, proprotein convertase subtilisin/kexin type 9, apolipoprotein B, and LDL receptor adaptor protein 1. His LDL cholesterol level was well controlled by the introduction of statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors. Cascade and reverse cascade screening identified his son and father as also having FH caused by this particular mutation.