Solanas–Barca M et al. – Rare APOE mutations are responsible for approximately 3.5% of familial combined hyperlipidemia (FCHL) cases in this population. APOE R136S and p.Leu149del induce autosomal dominant familial dysbetalipoproteinemia (FD) and a phenotype indistinguishable from FCHL, respectively.Methods
- In 279 unrelated subjects with FCHL in whom a functional LDLR mutation was excluded, sequencing of the entire APOE gene detected 9 carriers of a rare mutation: 5 subjects (1.8%) with the R136S mutation (arginine at residue 136 changed to serine) and 4 subjects (1.4%) with the p.Leu149del mutation, a 3–bp inframe deletion that results in the loss of leucine at position 149.
- Both genetic defects were detected with similar frequency (2.5% and 1.3%, respectively) in an independent group of 160 FCHL subjects from other locations in Spain.
- Family studies demonstrated cosegregation of these APOE mutations with hyperlipoproteinemia.
- R136S carriers showed dysbetalipoproteinemia, while the lipid phenotype of p.Leu149del carriers was IIa or IIb.