Background: Familial hypercholesterolemia (FH) is an autosomal dominant disorder caused by mutations in the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. Until now, molecular data concerning FH in Morocco is still limited. To gain more information in this field and to assess the contribution of these three genes in the cause of FH determinism, we analyzed six unrelated Moroccan probands and twenty-five of their family's members.
Methods: After LDLR and APOB genotype analysis, we screened the LDLR gene for mutations using southern blot and PCR-sequencing analysis. We also screened the APOB gene for the two common mutations R3500Q and R3531C by PCR-mediated site-directed mutagenesis. The PCSK9 gene was analyzed by direct sequencing.
Results: We identified three novel mutations (C25X, IVS3+5G>T, D558A) and two mutations previously described (D151N, A480E) in the LDLR gene. 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.
Conclusion: These data are in agreement with our previous study that suggests a heterogeneous mutational spectrum of FH in Morocco.