The R3500Q and R3531C mutations are absent in our probands and for 1 proband, the implication of LDLR, APOB and PCSK9 genes was excluded, supporting the implication of a fourth gene in the determination of FH.
Therefore, our results show that the family presents with familial hypercholesterolemia and give evidence that the R3531C substitution in the APOB gene is not an allelic variant leading to FDB.
The surprising result that only two mutations of apoB in the receptor-binding domain (Arg 3500 Gln and Arg 3531 Cys) were associated with defective LDL binding, hypercholesterolemia, or CAD is in stark contrast with familial hypercholesterolemia, where nearly 150 mutations of the LDL receptor have been described that disrupt its function.