We herein report the first Japanese case of familial hypercholesterolemia (FH) caused by a specific mutation in 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 PCSK9 inhibitors. Cascade and reverse cascade screening identified his son and father as also having FH caused by this particular mutation.
Keywords: APOE; LDLR; PCSK9; familial hypercholesterolemia.