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Mutational analysis of the LDLR gene in a cohort of Colombian families with familial hypercholesterolemia

      Highlights

      • p.W4X, p.D139G, and p.G396D mutations were identified in five Colombian families.
      • p.G396D mutation may be frequent in the Colombian population.
      • c.1187-1G > T variant accompanied the p.G396D mutation in three affected families.
      • 79% of the study population did not have mutation in the LDLR gene.

      Abstract

      Background and aims

      Familial hypercholesterolemia (FH) is characterized by elevated serum cholesterol levels due to high low-density lipoprotein (LDL) cholesterol levels. FH is an autosomal dominant genetic disorder and one of the most common dominant hereditary diseases in the world. However, the frequency of mutations in Colombia is unknown. The purpose of this preliminary study was to identify mutations in the LDL receptor (LDLR) gene in a Colombian population with FH.

      Methods

      The study included 24 families with clinical diagnosis of sure/probable FH. The 18 exons of the LDLR were sequenced by Sanger method.

      Results

      Among 18 variants identified, 3 were known pathogenic mutations and were identified in nine individuals in five unrelated families. Five affected individuals were heterozygous for one mutation each. They were the p.W4X in two, the p.D139G in two and the p.G396D in one. Two affected individuals were homozygous for p.G396D. The variant c.1187-1G > T, which has uncertain significance in FH pathogenesis, was present in all the individuals with the p.D139G mutation.

      Conclusions

      In total, 18 variants were identified, of which 14 correspond to known nonpathogenic variants. Three pathogenic variants were identified in the LDLR. No pathological mutations were identified in the LDLR in 79% of the study population.

      Keywords

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