Familial hypercholesterolemia in Morocco: first report of mutations in the LDL receptor gene

Abstract

Familial hypercholesterolemia (FH) is a genetic disorder mainly caused by defects in the low-density lipoprotein receptor (LDLR) gene, although it can also be due to alterations in the gene encoding apolipoprotein B (familial defective apoB or FDB) or in other unidentified genes. In Morocco, the molecular basis of FH is unknown. To obtain information on this issue, 27 patients with FH from eight unrelated families were analyzed by screening the LDLR (PCR-SSCP and Southern blot) and apoB genes (PCR and restriction enzyme digestion analysis). None of the patients carried either the R3500Q or the R3531C mutation in the apoB gene. By contrast, seven mutations in the LDLR gene were identified, including five missense mutations on exons 4, 6, 8, and 14 (C113R, G266C, A370T, P664L, C690S) and two large deletions (FH Morocco-1 and FH Morocco-2). The two major rearrangements and the missense mutation G266C are novel mutations and could well be causative of FH in the Moroccan population. This study has yielded preliminary information on the mutation spectrum of the LDLR gene among patients with FH in Morocco.

Transcriptomic Alterations in Lung Adenocarcinoma Unveil New Mechanisms Targeted by the TBX2 Subfamily of Tumor Suppressor Genes

“…T-box proteins are an evolutionary conserved family of transcription factors ( 11 ) that exhibits a lineage-specific role during embryogenesis by enhancing and/or repressing the transcriptional expression of a network of genes ( 12 ). TBX family members are sub-classified according to their sequence homology and pattern of expression ( 13 , 14 ).…”

Familial hypercholesterolemia associated with severe hypoalphalipoproteinemia in a Moroccan family

“…While the correlation between genotype and phenotype is clear in homozygotes, it is less evident in heterozygotes for FH. These results show the improved diagnostic precision obtained by introducing genetic diagnosis in FH families with identified mutation (Civeira 2004), even when the mutation spectrum of the LDLR gene in Moroccan population seems to be heterogeneous (El Messal et al 2003Chater et al 2006). Finally, further studies are needed to elucidate the molecular basis of the HALP observed in the studied family and the role of the reduced HDL-C levels in the development of atherosclerosis in a FH context.…”

“…LDLR gene: We analysed LDLR gene by Southern blot (El Messal et al 2003) and PCR-SSCP. For SSCP analysis, PCR products were added to 95% formamide buffer, denatured at 95 • C for 5 min, immediately chilled on ice and electrophoresed at 1050 V, at 25 • C or 15 • C in a MDE gel with or without 5% glycerol, respectively, in 0.6 × TBE buffer for 15 h, on an automated DNA sequencer equipped with a water jacket (ALF-Express TM , Pharmacia Biotech).…”

The A370T Variant (StuI Polymorphism) in the LDL Receptor Gene is not Associated with Plasma Lipid Levels or Cardiovascular Risk in UK Men

“…2004; Salazar et al . 2002; El Messal et al . 2003) have reported the detection of the 370T allele in FH patients, and have included these subjects in their mutation detection rate analysis, or in genotype‐phenotype analysis (Wang et al .…”