Failure of cosegregation between a rare STAP1 missense variant and hypercholesterolemia

Autosomal dominant familial hypercholesterolemia (FH) is characterized by elevated low-density lipoprotein cholesterol levels and an increased risk for atherosclerotic cardiovascular disease. Although rare pathogenic variants in genes encoding the low-density lipoprotein receptor, apolipoprotein B, proprotein convertase subtilisin/kexin 9 are found in more than 80% of molecularly defined patients with FH, a few rare minor causative genes have been proposed, including the gene encoding signal-transducing adaptor family member 1 (STAP1). Here, we describe a patient with hypercholesterolemia and the rare heterozygous missense variant p.D207N in STAP1. However, extending the pedigree showed failure of the variant to cosegregate with hypercholesterolemia, as both his sons were carriers of the variant and both were also normolipidemic. The findings add to the evidence against STAP1 as a genetic locus for FH.